1. Introduction
Epilepsy affects nearly 50 million people worldwide and is a disease that involves spontaneous frequent seizures caused by electrical disturbances in the brain (Bergen 1998; Meinardi, Scott et al. 2001). Epilepsy is a syndrome, or a collection of symptoms, in which people are predisposed to seizures (Fisher, van Emde Boas et al. 2005; Gomez-Alonso and Giraldez 2007; Jaseja 2009). Epilepsy diagnosis usually occurs after permanent injury to the brain or from inborn errors that cause brain tissue to become abnormally excited (Fisher, van Emde Boas et al. 2005). Health statistics show that children less than 2 and adults older than 65 are the most likely populations to develop epilepsy and that seizure events increase the risk of mortality in the individual (Feng 1978; Tsai 2005; Fountain, Van Ness et al. 2011). It is thought that nearly 4% of the US population will have seizure activity in their lifetimes, with many having seizures and never being aware they occurred.
In some types of epilepsy, the cause of the seizures cannot be clearly defined and does not present with other neurological disorders (Lerman, Sagie et al. 2011). Certain types of epilepsy have a genetic component (Poduri and Lowenstein 2011; Sisodiya and Mefford 2011; Sozmen, Baybas et al. 2011; Wilke, Worrell et al. 2011), but the most common diagnoses of epilepsy occur after neurological damage such as a stroke, transient ischemic attacks, a diagnosis of dementia, traumatic brain injury, brain abscesses, meningitis, encephalitis, neurosyphilis, brain tumors, hematomas, abnormal blood vessels, AIDS, congenital brain defects, metabolic diseases such as phenylketonuria, and liver or kidney failure.
Epileptic seizures range in severity from staring spells to violent convulsions and loss of consciousness (Haut, Lipton et al. 2005; Maillard, Vignal et al. 2009). Given the wide variety of factors that can precipitate epilepsy, it stands to reason that type of seizure is dependent on the location and type of the brain injury. Upon physical examination, many people suffering from epilepsy appear healthy (Maganti, Gerber et al. 2008). Most epileptics will present with clinical abnormal electrical activity as measured by an electroencephalograph (Urbach 2005). Epilepsy is further classified as idiopathic (presumed genetic basis), symptomatic (due to a structural abnormality) or cryptogenic (cause is undetermined) (Kwan and Brodie 2000; Berg and Kelly 2006; Farrell, Wirrell et al. 2006).
Unfortunately, after some epileptic events, there is a risk of neuron destruction. This is especially concerning due to the limited capacity of the brain to regenerate neurons and oftentimes, the damage is permanent. Following a seizure, epileptic’s brains often form excitotoxic lesions which destroy neurons by initiating apoptosis. The current treatment for epilepsy is limited to controlling the seizure activity. Anticonvulsants are oral medications used to prevent seizures in patients with epilepsy. The specific drug prescribed to patients varies based on their past seizure history and any underlying conditions that may have contributed to the epileptic diagnosis. (Prunetti and Perucca 2011; Steinert, Baier et al. 2011; Strzelczyk, Cenusa et al. 2011; Verrotti, Loiacono et al. 2011; Yasuda, Sugiura et al. 2011). In patients with epilepsy resulting from chronic infections, the epileptic symptoms will subside after the course of drug treatment. Also, epilepsy occurring after tumor development or following injury to blood vessels, such as a hematoma, can be successfully managed in some cases after the underlying cause of injury is treated. Nevertheless, it is difficult to treat these types of brain injuries; so many patients use proper medication to prevent the seizures (Sander 1993).
The cases of epilepsy that do not respond to medication (Go and Snead 2008; Berg 2009; Nakken and Tauboll 2009), are often candidates for invasive and risky procedures such as brain surgery. Surgery can remove the damaged cells of the brain which cause the abnormal electrical signals. Other surgical procedures such as implantation of a device, similar to a heart pacemaker, stimulate the vagal nerve and help reduce the frequency of seizures (Landre 2004). Unfortunately, there are also types of epilepsy that cannot be managed well with medication or any other available therapies and the general term for this type of epilepsy is called refractory or intractable epilepsy (Sander 1993; Kwan and Brodie 2000; Lerman, Sagie et al. 2011). Growing lines of evidence have indicated a role of inflammation in causing and exacerbating intractable epilepsy (Vezzani, French et al. 2011). Patients with intractable epilepsy often go on specialized diets which are thought to help reduce the severity and number of seizures. Popular diet choices for epileptic patients are diets low in carbohydrates, such as the ketogenic diet (Kossoff and McGrogan 2005), which is very low in carbohydrates and very high in fat but still calorie balanced for the individual. For undetermined reasons, when the body of an epileptic burns fat for fuel, rather than glucose, it can help control and prevent seizures (Baranano and Hartman 2008; Choragiewicz, Zarnowska et al. 2010; Westmark, Westmark et al. 2010). While the ketogenic diet is effective, long term health implications prevent patients from being on the diet for periods longer than two years (de Kinderen, Lambrechts et al. 2011). Dietary antioxidants are known to protect against seizures possibly by increasing the free radical scavenging capabilities of key antioxidant enzymes in the brain (Garjani, Fathiazad et al. 2009; Mehla, Reeta et al. 2010; Militao, Ferreira et al. 2010; Pages, Maurois et al. 2010; Sharma, Nehru et al. 2010; Tome Ada, Ferreira et al. 2010). Using a nutrigenomics approach to identify compounds with a beneficial effect (Suzuki 2011), researchers can identify genes associated with epilepsy susceptibility and then test whether particular dietary components, in this case selenium, can be used to improve the incidence, frequency, and severity of epilepsy and the resulting complications.
2. Selenium and selenoproteins
Selenium is a non-metal trace element discovered in 1817 as a by-product of sulfuric acid production (Brown and Arthur 2001). Selenium exists in nature in organic (such as selenomethionine and selenocysteine) or inorganic (such as selenate and selenite) forms (Puzanowska-Tarasiewicz, Kuzmicka et al. 2009).
Selenium can be incorporated non-specifically into methionone-rich proteins, such as those in the Brazil nut and sunflower seeds (Kortt, Caldwell et al. 1991). The biological functions of selenium are mainly mediated by selenoproteins, which contain selenocysteine (Allmang, Wurth et al. 2009; Lu and Holmgren 2009). Selenocysteine (Sec) has its own tRNA and its own codon, UGA (de Jesus, Hoffmann et al. 2006). Sec is inserted into mRNA in response to UGA codons in the genome of all selenoproteins. Selenoprotein mRNA is characterized by selenocysteine insertion sequence element (SECIS) (Howard, Moyle et al. 2007; Mix, Lobanov et al. 2007), and a RNA-binding protein complex (Bock, Forchhammer et al. 1991; Small-Howard and Berry 2005; Allmang and Krol 2006; Squires and Berry 2008). Some selenium-containing proteins such as the liver protein 56K and the liver fatty acid binding protein (Behne, Weiss-Nowak et al. 1994) can sequester Se, but they do not contain selenocysteine.
Selenium was only recognized as a toxicant (Belogorsky and Slaughter 1949; Fels and Cheldelin 1949; Klug, Harshfield et al. 1952; Mc and Portman 1952; Fabre and Truhaut 1956) and its biological role was unknown until 1952 when its essential role was discovered in microorganisms. It is a trace mineral that is essential for humans (Papp, Lu et al. 2007), which was first recognized when when dietary supplementation of selenium prevented liver necrosis in rats efficiently (Mertz and Schwarz 1958; Schwarz, Stesney et al. 1959; Schwarz, Porter et al. 1972). Following these studies, it was found that selenium was essential for glutathione peroxidase (GPX) activity (Flohe, Gunzler et al. 1973; Rotruck, Pope et al. 1973). Sec, now identified as the 21st amino acid was indentified in eubacteria and archaebacteria model systems (Ambrogelly, Palioura et al. 2007; Xu, Carlson et al. 2007). Stadtman and colleagues found that selenium was incorporated into proteins in the form of selenocysteine through labeled
Selenium deficiency (Kakturskii, Strochkova et al. 1990), or Keshan disease, is responsible for the cardiomyopathy in children living in parts of China where the soil lacks selenium (Guanqing 1979; Yang and Xia 1995; Yang, Chen et al. 2007). Recently, the gene of Secisbp2 protein, which is related with synthesis of selenoproteins (Copeland and Driscoll 1999; Copeland, Fletcher et al. 2000; Low, Grundner-Culemann et al. 2000; Tujebajeva, Copeland et al. 2000; Berry, Tujebajeva et al. 2001; Copeland and Driscoll 2001; Copeland, Stepanik et al. 2001; Fletcher, Copeland et al. 2001; Copeland and Driscoll 2002; Lescure, Allmang et al. 2002; Lescure, Fagegaltier et al. 2002), has been studied as a possible target for hereditary diseases, an example of which includes human thyroid hormone metabolism disorder (Dumitrescu, Liao et al. 2005). Selenium is also known as an important chemoprevention agent (El-Sayed, Aboul-Fadl et al. 2006; Micke, Schomburg et al. 2009) by inducing apoptosis in cancer cells (Jackson and Combs 2008) and senescence in the early stage of tumorigenesis (Wu, Kang et al. 2010) in a dose-dependent manner.
More than 50 years ago, the ROS (reactive oxygen species) theory of aging was proposed. However, there is still there is a lack of irrefutable evidence in support or opposition of this theory. ROS can be induced by exogenous sources, such as UV or ionizing irradiation (Finkel 2000), which are by-products of mitochondrial respiration and widespread
Most of the selenoproteins that have been identified are enzymes with selenium in their active sites. Through scanning the whole human genome to find SECIS, a total of 25 selenoproteins were discovered (Kryukov, Castellano et al. 2003), which contain five glutathione peroxidases (GPX1-4, GPX6), three thioredoxin reductases (TR1-3) (Hondal and Ruggles 2010), three iodothyronine deiodinases (DI-III), the 15-kDa selenoprotein (Sep 15), selenophosphate synthetase-2 (SPS2), and selenoprotein H, I, K, M, N, O, P, R, S, T, U, V. All selenoproteins only have one selenocysteine residue except for selenoprotein P which contains 10 residues (Burk and Hill 1999). The domains containing selenocysteine residues in selenoprotein are highly related with their enzyme activities (Hill, Zhou et al. 2007). It was noted that cysteine replacing the selenocysteine residue in selenoproteins lead to reduction of catalytic activity (Hazebrouck, Camoin et al. 2000; Lee, Bar-Noy et al. 2000; Korotkov, Novoselov et al. 2002; Kryukov and Gladyshev 2002).
Notably, more than one-third of selenoproteins play a critical role in combating oxidative stress. The GPX family uses glutathione as a reducing equivalent to eliminate hydrogen peroxide, organic hydroperoxides and phospholipid hydroperoxides (Bosch-Morell, Flohe et al. 1999; Flohe, Hecht et al. 1999). The redox status of thioredoxin is under the control of the thioredoxin reductase (TR) family (Bjornstedt, Hamberg et al. 1995; Holmgren and Bjornstedt 1995). Sel P is thought to be not only a selenium carrier, which distributes in body fluids, but capable of eliminating phospholipid hydroperoxides (Saito, Hayashi et al. 1999; Takebe, Yarimizu et al. 2002). It is important to elucidate the mechanism by which selenoperoxidases eliminate ROS in the brain and to identify additional selenoperoxidases and their functions during aging and neuron degeneration.
3. Selenium and selenoproteins in epilepsy
The brain expresses most selenoproteins and is at the apex of selenium retention in the body (Nakayama, Hill et al. 2007). It is proposed that selenium may be necessary for prevention of epilepsy or other degenerative neurological disorders; however, there is no consensus in the field whether selenium plays a direct role or not. Selenium has a role in protection the neurons from excitotoxic insults, such as the continuous stimulation of a nerve cell by glutamate or another neurotransmitter, and thus can decrease the insult burden on the neurons (Savaskan, Brauer et al. 2003).
Although no severe neurological phenotypes have been associated with a selenium deficient diet, this may be due to the brain’s preferential sequestration of body selenium. Mice on a selenium deficient diet are, however, more susceptible to neuropathological changes (Hill, Zhou et al. 2004). It is not well known how selenium status in the blood and the brain are correlated (Chen and Berry 2003), but it is known that selenium supplementation can prevent dopamine loss and degeneration of neurons in the substantia nigra, and reduce lipid peroxidation (Aldeeb, Almoutaery et al. 1995; Imam, Newport et al. 1999; Zafar, Siddiqui et al. 2003). Selenium was shown to protect the neurons through selenoproteins (Savaskan, Brauer et al. 2002; Lamarche, Signorini-Allibe et al. 2004; Reeves, Bellinger et al. 2010; Wang, Geng et al. 2010) and other studies that combine selenium treatment with anticonvulsant medication showed a synergistic protective effect against induced seizures (Kutluhan, Naziroglu et al. 2009). Also, in cases of selenium deficiency, neurons are exposed to increased glutamate-induced excitotoxicity because selenium has an inhibitory effect on the glutamate induced NF-B and AP-1 activation (Savaskan, Brauer et al. 2002; Santamaria, Vazquez-Roman et al. 2005).
There are a total of 24 selenoproteins in mice, all of which are expressed in the brain, particularly in neurons of the olfactory bulb, hippocampus, cerebral cortex and cerebellar cortex (Zhang, Zhou et al. 2008). In these tissues
There are some regions of the rodent brain that express significantly lower levels of selenoproteins, which implies that some structures of the brain are less dependent on selenium availability. Selenoprotein genes are expressed the lowest in the oculomotor nucleus, Edinger-Westphal nucleus, nucleus Raphé pontis, anteroventral periventricular nucleus and dorsal premammillary nucleus; however, these brain regions do express the same selenoproteins that are found to be highly expressed in other regions of the brain, but at a significantly lower level, such as
Generation of ROS and the resulting oxidative stress are known to be both the cause and consequence of many neurodegenerative conditions (Sander 1993). Post mortem autopsies of people with the neurodegenerative disorders Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis all show that there are increased ROS in the regions of the brains that were affected by the neurodegenerative disorder. The brain has a reduced capacity for regeneration and a high metabolic rate which predisposes it to oxidative damage. The repair mechanisms that the cells have employed to counteract oxidative damage are primarily antioxidant enzymes such as glutathione peroxidases and thioredoxin reductases which are dependent on selenium for their function. Accumulating lines of evidence suggest that selenium-dependent antioxidant enzymes and selenoproteins are integral to epilepsy and have a role in the progression of the disease. It is promising to use selenium as a line of treatment against degenerative free radical diseases such as epilepsy.
3.1. The Se-dependent glutathione peroxidase
The function of the GPX family is to remove hydrogen and other peroxides from the brain and other tissues by coupling its reduction to water and alcohols using glutathione as a reducing equivalent. Glutathione is found in the mitochondria and cytoplasm of brain tissue and has been found to be released into the extracellular space by astrocytes. Interestingly, the first report of selenium status affecting any neurological condition was in infants with intractable epilepsy (Weber, Maertens et al. 1991). Infant brains are particularly susceptible to oxidative damage, which can contribute to abnormal brain electrical signaling, because of the high concentration of unsaturated fatty acids in the infant brain needed to synthesize cholesterol and fatty acids. These nutrients are necessary for the billions of developing nerve connections.
The seizure symptoms of these infants can be reversed with selenium supplementation (Weber, Maertens et al. 1991; Ramaekers, Calomme et al. 1994). Children suffering from intractable epilepsy are deficient in glutathione peroxidase activity. From the four children studied, two had normal blood selenium and high concentrations of GPX in their plasma, but low enzymatic activity. The other children had low intracellular selenium levels and low GPX expression and activity. Selenium supplementation and discontinuation of their anticonvulsant medication decreased seizure activity. The second study found that oral selenium supplements in children (3-5 g/kg body weight) decreased frequency of seizures, improved electroencephalograph recordings, and restored liver function in the infants after two weeks of treatment (Ramaekers, Calomme et al. 1994). It was thought that supplementation of selenium restored the function of selenium-dependent GPX1 and GPX4 activity. From these results, selenium status is an important triggering factor for the onset of intractable seizures and that selenium-conferred antioxidant protection in the brain can help prevent neuronal damage following frequent seizures.
It has been suggested that treatment with anticonvulsants, such as valproic acid, which induces oxidative stress, depletes total body selenium and decreases GPX activity (Naziroglu 2009). However, others believe that selenium supplementation in congruence with antiepileptic drugs increase the risk of systemic toxicity. The conflicting selenium levels are likely associated with the pharmacology of the particular drug, duration of treatment, age of subject, validity of plasma selenium estimating brain selenium concentrations, and the underlying cause of the patient’s epilepsy. It has been found that epileptic patients, without medication, have lower blood and tissue levels of selenium in addition to lower levels of selenoproteins and lower levels of selenium-dependent redox enzymes. In particular, intractable epileptics have been shown to have significantly lower mean serum selenium levels compared to a control group (Ashrafi, Shabanian et al. 2007). Animal models have shown that selenium can prevent the development of iron-induced epileptic symptoms due to selenium’s ability to combat peroxidative injury (Rubin and Willmore 1980; Willmore and Rubin 1981).
3.2. Thioredoxin reductases
Thioredoxin reductases (TR) use NADPH for reduction of thioredoxin in various cellular redox pathways (Tamura and Stadtman 2002). TR-3 is expressed in very low levels in the mouse brain (Zhang, Zhou et al. 2008). Although TR-1 is well characterized and expressed in high levels in other organs, it is not highly expressed in the brain. Since TR is important for intracellular redox regulation and antioxidant defense (Schweizer, Brauer et al. 2004), decreased TR expression and activities could lead to enhanced cell loss, thus increasing the risk for epilepsy and other neurodegenerative conditions.
3.3. Selenoprotein P
Selenoprotein P (Sel P) is unique because it contains 10-17 selenocysteine residues, unlike other selenoproteins which contain only one. Sel P is produced mostly in the liver, but all tissues make and secrete Sel P into the plasma (Burk and Hill 2005; Hoffmann, Hoge et al. 2007). In rodents, Sel P is a predominant form of selenium in the plasma. Sel P is responsible for selenium transportation throughout the body, particularly to the brain where selenium is needed for incorporation into other selenoproteins which confer antioxidant benefits (Hill, Zhou et al. 2007). Sel P knockout mice develop seizures and movement disorders when raised on selenium restricted diets.
During seizure activity in epileptics, the neurons in the affected areas of the brain often have redox shifts due to the large influx of calcium through voltage gated channels (Stefani, Spadoni et al. 1997). If cellular redox equilibrium is not quickly restored following seizures, it is probable that the neurons will die and that region of the brain will be unable to function properly (Wirth, Conrad et al. 2010). It is thought that selenium, probably through its function in the GPX or TR families, can help prevent neuronal cell death and neutralize ROS which is generated as a consequence of high intracellular calcium (Xiong, Markesbery et al. 2007). Typically the brain can handle redox shifts and occasional electrolyte imbalances; however, during a seizure these activities happen at a rate and frequency that the cells cannot handle (Howse and Duffy 1975). The neurons eventually will die, and cause an increase in potentially harmful cellular byproducts (Barinaga 1998).
3.4. Selenoprotein W
Selenoprotein W (Sel W) has a redox motif and binds glutathione (Beilstein, Vendeland et al. 1996; Whanger 2009), similar to the well characterized GPX family. The ‘W’ designation is because of the white muscle disease seen in grazing livestock in areas where the soil is depleted of selenium (Vendeland, Beilstein et al. 1993). Sel W is highly expressed in the four basic brain regions in rodents; the hippocampus, olfactory area, cerebellar cortex, and isocortex (Zhang, Zhou et al. 2008).
The expression of Sel W is induced in the neurons of mesial temporal lobe epilepsy patients more than tenfold and is associated with BCL2 expression, which suggests that the Sel W induction is a defensive response to oxidative stress (Yuzbasioglu, Karatas et al. 2009). Furthermore, the expression of Sel W in cortex, cerebellum, and thalamus remains constant under Se deficiency (Sun et al., 2001b). Thus, Sel W expression is maintained in certain regions of the brain under selenium deficiency, suggesting a critical role of Sel W in the protection against seizure activities that is associated with increased oxidative stress.
3.5. Selenoprotein H
Selenoprotein H (Sel H) is a nucleolar DNA-binding protein (Novoselov, Kryukov et al. 2007) and may function as a transcription factor (Panee, Stoytcheva et al. 2007). It has been found that Sel H mRNA is highly expressed in the hippocampus during development but level falls quickly after birth and is undetectable in the adult brain (Zhang, Zhou et al. 2008); however, in another study the Sel H gene was found to be expressed in the adult mouse brain by using the RT-PCR method (Hoffmann, Hoge et al. 2007).
3.6. Selenoprotein M
Selenoprotein M (Sel M) is a small endoplasmic reticulum protein with unknown function, which is highly expressed in cornu ammonis granule cells of dentate gyrus (Zhang, Zhou et al. 2008). Cornu ammonis is also known as Ammon’s horn and is part of the interlocking gyri which makes up the hippocampus. Interestingly, the most common form of neuropathological damage in temporal lobe epilepsy patients is sclerosis (hardening of tissue) of the cornu ammonis, also known as Ammon’s horn sclerosis, which is characterized by neuronal cell loss in the hippocampus region of the brain. Common clinical markers of the disease include granule cell dispersion, reactive gliosis, and the segmental loss of pyramidal neurons. Unfortunately, 65% of people with temporal lobe epilepsy suffer from this disease (Blumcke, Thom et al. 2002; de Lanerolle and Lee 2005). Many of the seizures due to temporal lobe epilepsy are very poorly controlled with anticonvulsant drugs. The role of Sel M is not fully understood and it is unclear whether Ammon’s horn sclerosis is the cause of seizures of epileptics, or rather damage from the ongoing seizure activity.
4. Selenium and neurological disorders
Most inherited or congenital forms of epilepsy develop and occur before the age of 2. Older adults who have developed epilepsy have done so mostly because of brain injuries (hematomas and other bleeding vessels) or after a stroke. Generally, the most common cause of epilepsy in the elderly is attributed to cerebrovascular diseases or prescription drug reactions. Older populations are more at risk for drugs causing epileptiform activities because of their increased sensitivity to all drugs due to decreased drug metabolism.
Also other diseases in the elderly, particularly those that cause impaired language function or overall neurological deterioration, have been associated with increased seizure risks. Other factors such as metabolic problems, uraemia, thyroid problems, low blood sugar, electrolyte imbalances and liver damage can all contribute to seizures in the older population. In addition to the metabolic risk factors, epilepsy risk can also increase in patients with neurological disorders such as Alzheimer’s (Noebels 2011), down syndrome, and dementia (Ito, Echizenya et al. 2009; Palop and Mucke 2009; Rao, Dove et al. 2009; Scarmeas, Honig et al. 2009; Larner 2010; Westmark, Westmark et al. 2010).
There is a link between neurological disorders and aging (Zhang, Rocourt et al. 2010). Since the body preferentially retains selenium in the brain even during periods of selenium deficiency, which further implies that selenium plays an important role in the brain (Behne, Hilmert et al. 1988; Chen and Berry 2003). Neurological disorders such as Alzheimer’s disease, Parkinson’s disease, and those disease states resulting from damage caused by environmental toxins, ischemic insults, drug abuse, and brain tumors are exacerbated by ROS (Chen and Berry 2003).
The selenium protection against neurological disorders is primarily conferred through antioxidative selenoproteins (Zhang, Rocourt et al. 2010). Therefore, selenoproteins play an important role in regulating redox reactions in the body, and particularly the brain. For example, the brains in mouse models of Alzheimer’s disease show reduced levels of Sel M, which could mean that this selenoprotein plays a protective role in the development of Alzheimer’s disease (Hwang, Cho et al. 2005).
Sel P knockout mice have movement disorders and seizures when given selenium-restricted diets from their birth (Hill, Zhou et al. 2003; Schomburg, Schweizer et al. 2003; Kutluhan, Naziroglu et al. 2009). Rats on selenium deficient diets have an increased risk of seizures and neuronal loss, further providing evidence that selenium can help prevent seizures. Because epilepsy is characterized by neuronal loss resulting from pro-apoptotic factors in association with oxidative stress (Savaskan, Brauer et al. 2003), selenium might help alleviate the underlying causes of brain injury that precipitate seizures.
5. Nutrigenomics perspectives
There is much evidence that speculates on the genetic aspect of epilepsy (Rees 2010; Sisodiya and Mefford 2011). Nonetheless, since epilepsy is a syndrome and not a disease, the cause of seizures in epileptics varies widely. Furthermore, even if epilepsy could be divided into groups based on the respective, underlying cause, it would still be difficult to determine the genetic influence because of changes across clinical subgroups and amongst families. However, some types of epilepsy have been shown to have strong genetic components (Greenberg and Subaran 2011): 1) partial epilepsy has been linked to chromosome 10 q; 2) benign familial neonatal convulsions have been mapped to chromosome 20 q and another locus found on 8q; 3) a progressive form of myoclonus epilepsy has been localized to chromosome 21 q; 4) juvenile myoclonic epilepsy has been associated with regions of chromosome 6. Interestingly, the types of epilepsy syndromes that have genetic linkage evidence are a very small proportion of all epilepsy cases and no genetic basis has been found for most types of epilepsy.
Nutrigenomics is the study of how nutrition impacts the variation of gene expression across individuals. Seeing as how genetically diverse individuals are, it would stand to reason that individualized diets based on a person’s genetic background can contribute to better overall health. Nutrigenomic approaches will become increasingly necessary in treating chronic diseases, including epilepsy. In the future it is expected that we will uncover genetic evidence that explains why certain people have different responses to similar diet, and how such variations help alleviate neuronal disorders.
References
- 1.
Aldeeb S. Almoutaery K. et al. 1995 Neuroprotective Effect of Selenium on Iminodipropionitrile-Induced Toxicity." Journal of Psychiatry & Neuroscience20 3 189 192 - 2.
Allmang C. Krol A. 2006 Selenoprotein synthesis: UGA does not end the story." Biochimie88 11 1561 71 - 3.
Allmang C. Wurth L. et al. 2009 The selenium to selenoprotein pathway in eukaryotes: more molecular partners than anticipated." Biochim Biophys Acta1790 11 1415 23 - 4.
Ambrogelly A. Palioura S. et al. 2007 Natural expansion of the genetic code." Nat Chem Biol3 1 29 35 - 5.
Ashrafi M. R. Shabanian R. et al. 2007 Selenium and intractable epilepsy: Is there any correlation?" Pediatric Neurology36 1 25 29 - 6.
Axley M. J. Stadtman T. C. 1989 Selenium metabolism and selenium-dependent enzymes in microorganisms." Annu Rev Nutr9 127 37 - 7.
Baranano K. W. Hartman A. L. 2008 The ketogenic diet: uses in epilepsy and other neurologic illnesses." Curr Treat Options Neurol10 6 410 9 - 8.
Barinaga M. 1998 Stroke-damaged neurons may commit cellular suicide." Science281 5381 1302 3 - 9.
Behne D. Hilmert H. et al. 1988 Evidence for specific selenium target tissues and new biologically important selenoproteins." Biochim Biophys Acta966 1 12 21 - 10.
Behne D. Weiss-Nowak C. et al. 1994 Application of nuclear analytical methods in the investigation and identification of new selenoproteins." Biol Trace Elem Res 43-45: 287-97. - 11.
Beilstein M. A. Vendeland S. C. et al. 1996 Selenoprotein W of rat muscle binds glutathione and an unknown small molecular weight moiety." J Inorg Biochem61 2 117 24 - 12.
Belogorsky J. B. Slaughter D. 1949 Administration of BAL in selenium poisoning." Proc Soc Exp Biol Med72 1 196 8 - 13.
Berg A. T. 2009 Identification of pharmacoresistant epilepsy." Neurol Clin27 4 1003 13 - 14.
Berg A. T. Kelly M. M. 2006 Defining intractability: comparisons among published definitions." Epilepsia47 2 431 6 - 15.
Bergen D. C. 1998 Preventable neurological diseases worldwide." Neuroepidemiology17 2 67 73 - 16.
Berry M. J. Tujebajeva R. M. et al. 2001 Selenocysteine incorporation directed from the 3’UTR: characterization of eukaryotic EFsec and mechanistic implications." Biofactors 14(1-4): 17-24. - 17.
Bjornstedt M. Hamberg M. et al. 1995 Human thioredoxin reductase directly reduces lipid hydroperoxides by NADPH and selenocystine strongly stimulates the reaction via catalytically generated selenols." Journal of Biological Chemistry270 20 11761 4 - 18.
Blumcke I. Thom M. et al. 2002 Ammon’s horn sclerosis: a maldevelopmental disorder associated with temporal lobe epilepsy." Brain Pathol12 2 199 211 - 19.
Bock A. Forchhammer K. et al. 1991 Selenocysteine: the 21st amino acid." Mol Microbiol5 3 515 20 - 20.
Bosch-Morell F. Flohe L. et al. 1999 4 Hydroxynonenal inhibits glutathione peroxidase: protection by glutathione." Free Radic Biol Med 26(11-12): 1383-7. - 21.
Brown K. M. Arthur J. R. 2001 Selenium, selenoproteins and human health: a review." Public Health Nutr 4(2B):593 9 - 22.
Burk R. F. Hill K. E. 1999 Orphan selenoproteins." Bioessays21 3 231 7 - 23.
Burk R. F. Hill K. E. 2005 Selenoprotein P: an extracellular protein with unique physical characteristics and a role in selenium homeostasis." Annu Rev Nutr25 215 35 - 24.
Chambers I. Frampton J. et al. 1986 The structure of the mouse glutathione peroxidase gene: the selenocysteine in the active site is encoded by the ‘termination’ codon, TGA." EMBO J5 6 1221 7 - 25.
Chen J. Berry M. J. 2003 Selenium and selenoproteins in the brain and brain diseases." Journal of Neurochemistry86 1 1 12 - 26.
Cheng W. H. Ho Y. S. et al. 1997 Overexpression of cellular glutathione peroxidase does not affect expression of plasma glutathione peroxidase or phospholipid hydroperoxide glutathione peroxidase in mice offered diets adequate or deficient in selenium." Journal of Nutrition127 5 675 80 - 27.
Cheng W. H. Ho Y. S. et al. 1997 Cellular glutathione peroxidase knockout mice express normal levels of selenium-dependent plasma and phospholipid hydroperoxide glutathione peroxidases in various tissues." Journal of Nutrition127 8 1445 50 - 28.
Choragiewicz T. Zarnowska I. et al. 2010 Anticonvulsant and neuroprotective effects of the ketogenic diet]." Przegl Lek67 3 205 12 - 29.
Cone J. E. Del Rio R. M. et al. 1976 Chemical characterization of the selenoprotein component of clostridial glycine reductase: identification of selenocysteine as the organoselenium moiety." Proc Natl Acad Sci U S A73 8 2659 63 - 30.
Copeland P. R. Driscoll D. M. 1999 Purification, redox sensitivity, and RNA binding properties of SECIS-binding protein 2, a protein involved in selenoprotein biosynthesis." Journal of Biological Chemistry274 36 25447 54 - 31.
Copeland P. R. Driscoll D. M. 2001 RNA binding proteins and selenocysteine." Biofactors 14(1-4): 11-6. - 32.
Copeland P. R. Driscoll D. M. 2002 Purification and analysis of selenocysteine insertion sequence-binding protein 2." Methods Enzymol347 40 9 - 33.
Copeland P. R. Fletcher J. E. et al. 2000 A novel RNA binding protein, SBP2, is required for the translation of mammalian selenoprotein mRNAs." EMBO J19 2 306 14 - 34.
Copeland P. R. Stepanik V. A. et al. 2001 Insight into mammalian selenocysteine insertion: domain structure and ribosome binding properties of Sec insertion sequence binding protein 2." Mol Cell Biol21 5 1491 8 - 35.
de Jesus L. A. Hoffmann P. R. et al. 2006 Nuclear assembly of UGA decoding complexes on selenoprotein mRNAs: a mechanism for eluding nonsense-mediated decay?" Mol Cell Biol26 5 1795 805 - 36.
de Kinderen R. J. Lambrechts D. A. et al. 2011 Research into the (Cost-) effectiveness of the ketogenic diet among children and adolescents with intractable epilepsy: design of a randomized controlled trial." BMC Neurol 11(1): 10. - 37.
de Lanerolle N. C. Lee T. S. 2005 New facets of the neuropathology and molecular profile of human temporal lobe epilepsy." Epilepsy Behav7 2 190 203 - 38.
Dreher I. Schmutzler C. et al. 1997 Expression of selenoproteins in various rat and human tissues and cell lines." Journal of Trace Elements in Medicine and Biology11 2 83 91 - 39.
Dumitrescu A. M. Liao X. H. et al. 2005 Mutations in SECISBP2 result in abnormal thyroid hormone metabolism." Nat Genet37 11 1247 52 - 40.
El -Sayed W. M. Aboul-Fadl T. et al. 2006 Effect of selenium-containing compounds on hepatic chemoprotective enzymes in mice." Toxicology 220(2-3): 179-88. - 41.
Fabre R. Truhaut R. 1956 Toxicological study of selenium." Rev Pathol Gen Physiol Clin56 675 323 39 - 42.
Farrell K. Wirrell E. et al. 2006 The definition and prediction of intractable epilepsy in children." Adv Neurol97 435 42 - 43.
Fels I. G. Cheldelin V. H. 1949 Selenate inhibition studies; the role of sulfate in selenate toxicity in yeast." Arch Biochem22 3 402 5 - 44.
Feng Y. K. 1978 Some statistics on 2,810 cases of epilepsy." Chin Med J (Engl)4 6 449 56 - 45.
Finkel T. 2000 Redox-dependent signal transduction." FEBS Lett 476(1-2): 52-4. - 46.
Fisher R. S. van Emde W. Boas et. al 2005 Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE)." Epilepsia46 4 470 2 - 47.
Fletcher J. E. Copeland P. R. et al. 2001 The selenocysteine incorporation machinery: interactions between the SECIS RNA and the SECIS-binding protein SBP2." RNA7 10 1442 53 - 48.
Flohe L. Gunzler W. A. et al. 1973 Glutathione peroxidase: a selenoenzyme." FEBS Lett32 1 132 4 - 49.
Flohe L. Hecht H. J. et al. 1999 Glutathione and trypanothione in parasitic hydroperoxide metabolism." Free Radic Biol Med 27(9-10): 966-84. - 50.
Fountain N. B. Van Ness P. C. et al. 2011 Quality improvement in neurology: AAN epilepsy quality measures: Report of the Quality Measurement and Reporting Subcommittee of the American Academy of Neurology." Neurology76 1 94 9 - 51.
Garjani A. Fathiazad F. et al. 2009 The effect of total extract of Securigera securidaca L. seeds on serum lipid profiles, antioxidant status, and vascular function in hypercholesterolemic rats." J Ethnopharmacol126 3 525 32 - 52.
Go C. Snead O. C. 3rd 2008 Pharmacologically intractable epilepsy in children: diagnosis and preoperative evaluation." Neurosurg Focus 25(3): E2. - 53.
Gomez-Alonso J. Giraldez B. G. 2007 Epilepsy: a new definition for an old disease." Rev Neurol45 2 126 7 - 54.
Greenberg D. A. Subaran R. 2011 Blinders, phenotype, and fashionable genetic analysis: a critical examination of the current state of epilepsy genetic studies." Epilepsia52 1 1 9 - 55.
Guanqing H. 1979 On the etiology of Keshan disease: two hypotheses." Chin Med J (Engl)92 6 416 22 - 56.
Haut S. R. Lipton R. B. et al. 2005 Identifying seizure clusters in patients with epilepsy." Neurology65 8 1313 5 - 57.
Hawkes W. C. Alkan Z. 2010 Regulation of redox signaling by selenoproteins." Biol Trace Elem Res134 3 235 51 - 58.
Hazebrouck S. Camoin L. et al. 2000 Substituting selenocysteine for catalytic cysteine 41 enhances enzymatic activity of plant phospholipid hydroperoxide glutathione peroxidase expressed in Escherichia coli." Journal of Biological Chemistry275 37 28715 21 - 59.
Hill K. E. Zhou J. et al. 2007 The selenium-rich C-terminal domain of mouse selenoprotein P is necessary for the supply of selenium to brain and testis but not for the maintenance of whole body selenium." Journal of Biological Chemistry282 15 10972 80 - 60.
Hill K. E. Zhou J. et al. 2003 Deletion of selenoprotein P alters distribution of selenium in the mouse." Journal of Biological Chemistry278 16 13640 6 - 61.
Hill K. E. Zhou J. et al. 2004 Neurological dysfunction occurs in mice with targeted deletion of the selenoprotein P gene." Journal of Nutrition134 1 157 61 - 62.
Hoffmann P. R. Hoge S. C. et al. 2007 The selenoproteome exhibits widely varying, tissue-specific dependence on selenoprotein P for selenium supply." Nucleic Acids Research35 12 3963 73 - 63.
Hoffmann P. R. Hoge S. C. et al. 2007 The selenoproteome exhibits widely varying, tissue-specific dependence on selenoprotein P for selenium supply." Nucleic Acids Research35 12 3963 3973 - 64.
Holmgren A. Bjornstedt M. 1995 Thioredoxin and thioredoxin reductase." Methods Enzymol252 199 208 - 65.
Hondal R. J. Ruggles E. L. 2011 Differing views of the role of selenium in thioredoxin reductase." Amino Acids41 1 73 89 - 66.
Howard M. T. Moyle M. W. et al. 2007 A recoding element that stimulates decoding of UGA codons by Sec tRNA[Ser]Sec." RNA13 6 912 20 - 67.
Howse D. C. Duffy T. E. 1975 Control of the redox state of the pyridine nucleotides in the rat cerebral cortex. Effect of electroshock-induced seizures." J Neurochem24 5 935 40 - 68.
Hwang D. Y. Cho J. S. et al. 2005 Differentially expressed genes in transgenic mice carrying human mutant presenilin-2 (N141I): correlation of selenoprotein M with Alzheimer’s disease." Neurochem Res30 8 1009 19 - 69.
Imam S. Z. Newport G. D. et al. 1999 Selenium, an antioxidant, protects against methamphetamine-induced dopaminergic neurotoxicity." Brain Research818 2 575 578 - 70.
Ito M. Echizenya N. et al. 2009 A case series of epilepsy-derived memory impairment resembling Alzheimer disease." Alzheimer Dis Assoc Disord23 4 406 9 - 71.
Jackson M. I. Combs G. F. Jr 2008 Selenium and anticarcinogenesis: underlying mechanisms." Curr Opin Clin Nutr Metab Care11 6 718 26 - 72.
Jaseja H. 2009 Definition of epilepsy: significance of its revision on clinical neurophysiological basis to improve prognosis and quality of life of patients with epilepsy." Med Hypotheses72 6 756 7 - 73.
Kakturskii L. V. Strochkova L. S. et al. 1990 Hyposelenoses." Arkh Patol52 12 3 8 - 74.
Klug H. L. Harshfield R. D. et al. 1952 Methionine and selenium toxicity." Journal of Nutrition48 4 409 20 - 75.
Korotkov K. V. Novoselov S. V. et al. 2002 Mammalian selenoprotein in which selenocysteine (Sec) incorporation is supported by a new form of Sec insertion sequence element." Mol Cell Biol22 5 1402 11 - 76.
Kortt A. A. Caldwell J. B. et al. 1991 Amino acid and cDNA sequences of a methionine-rich 2S protein from sunflower seed (Helianthus annuus L.)." Eur J Biochem195 2 329 34 - 77.
Kossoff E. H. Mc Grogan J. R. 2005 Worldwide use of the ketogenic diet." Epilepsia46 2 280 9 - 78.
Kryukov G. V. Castellano S. et al. 2003 Characterization of mammalian selenoproteomes." Science300 5624 1439 43 - 79.
Kryukov G. V. Gladyshev V. N. 2002 Mammalian selenoprotein gene signature: identification and functional analysis of selenoprotein genes using bioinformatics methods." Methods Enzymol347 84 100 - 80.
Kutluhan S. Naziroglu M. et al. 2009 Effects of selenium and topiramate on lipid peroxidation and antioxidant vitamin levels in blood of pentylentetrazol-induced epileptic rats." Biol Trace Elem Res 129(1-3): 181-9. - 81.
Kwan P. Brodie M. J. 2000 Early identification of refractory epilepsy." New England Journal of Medicine342 5 314 319 - 82.
Ladiges W. Van Remmen H. et al. 2009 Lifespan extension in genetically modified mice." Aging Cell8 4 346 52 - 83.
Lamarche F. Signorini-Allibe N. et al. 2004 Influence of vitamin E, sodium selenite, and astrocyte-conditioned medium on neuronal survival after chronic exposure to ethanol." Alcohol33 2 127 38 - 84.
Landre E. 2004 Vagus nerve stimulation and refractory partial epilepsies]." Rev Neurol (Paris) 160 Spec1 S280 7 - 85.
Larner A. J. 2010 Epileptic seizures in AD patients." Neuromolecular Med12 1 71 7 - 86.
Lee B. J. Worland P. J. et al. 1989 Identification of a selenocysteyl-tRNA(Ser) in mammalian cells that recognizes the nonsense codon, UGA." Journal of Biological Chemistry264 17 9724 7 - 87.
Lee S. R. Bar-Noy S. et al. 2000 Mammalian thioredoxin reductase: oxidation of the C-terminal cysteine/selenocysteine active site forms a thioselenide, and replacement of selenium with sulfur markedly reduces catalytic activity." Proc Natl Acad Sci U S A97 6 2521 6 - 88.
Lei X. G. Cheng W. H. et al. 2007 Metabolic regulation and function of glutathione peroxidase-1." Annu Rev Nutr27 41 61 - 89.
Leinfelder W. Stadtman T. C. et al. 1989 Occurrence in vivo of selenocysteyl-tRNA(SERUCA) in Escherichia coli. Effect of sel mutations." Journal of Biological Chemistry264 17 9720 3 - 90.
Lerman P. Sagie S. et al. 2011 Why can seizures remain intractable? Clinical vignettes from the life experience of a pediatric epileptologist." J Child Neurol26 1 121 5 - 91.
Lescure A. Allmang C. et al. 2002 cDNA cloning, expression pattern and RNA binding analysis of human selenocysteine insertion sequence (SECIS) binding protein 2." Gene 291(1-2): 279-85. - 92.
Lescure A. Fagegaltier D. et al. 2002 Protein factors mediating selenoprotein synthesis." Curr Protein Pept Sci3 1 143 51 - 93.
Low S. C. Grundner-Culemann E. et al. 2000 SECIS-SBP2 interactions dictate selenocysteine incorporation efficiency and selenoprotein hierarchy." EMBO J19 24 6882 90 - 94.
Lu J. Holmgren A. 2009 Selenoproteins." Journal of Biological Chemistry284 2 723 7 - 95.
Maganti R. Gerber P. et al. 2008 Nonconvulsive status epilepticus." Epilepsy Behav12 4 572 86 - 96.
Maillard L. Vignal J. P. et al. 2009 Risk of epilepsy after a first epileptic seizure in adults: Can we predict the future?." Rev Neurol (Paris)165 10 782 8 - 97.
Mc C. K. Portman O. W. 1952 Toxicity of dimethyl selenide in the rat and mouse." Proc Soc Exp Biol Med79 2 230 1 - 98.
Mehla J. Reeta K. H. et al. 2010 Protective effect of curcumin against seizures and cognitive impairment in a pentylenetetrazole-kindled epileptic rat model." Life Sci 87(19-22): 596-603. - 99.
Meinardi H. Scott R. A. et al. 2001 The treatment gap in epilepsy: the current situation and ways forward." Epilepsia42 1 136 49 - 100.
Mertz W. Schwarz K. 1958 Reversal of respiratory decline in necrotic liver degeneration by intraportal antioxidants." Proc Soc Exp Biol Med98 4 808 12 - 101.
Micke O. Schomburg L. et al. 2009 Selenium in oncology: from chemistry to clinics." Molecules14 10 3975 88 - 102.
Militao G. C. Ferreira P. M. et al. 2010 Effects of lipoic acid on oxidative stress in rat striatum after pilocarpine-induced seizures." Neurochem Int56 1 16 20 - 103.
Mix H. Lobanov A. V. et al. 2007 SECIS elements in the coding regions of selenoprotein transcripts are functional in higher eukaryotes." Nucleic Acids Research35 2 414 23 - 104.
Nakayama A. Hill K. E. et al. 2007 All regions of mouse brain are dependent on selenoprotein P for maintenance of selenium." Journal of Nutrition137 3 690 693 - 105.
Nakken K. O. Tauboll E. 2009 Drug-resistant epilepsy." Tidsskr Nor Laegeforen129 19 1986 9 - 106.
Naziroglu M. 2009 Role of Selenium on Calcium Signaling and Oxidative Stress-induced Molecular Pathways in Epilepsy." Neurochem Res34 12 2181 91 - 107.
Noebels J. 2011 A perfect storm: Converging paths of epilepsy and Alzheimer’s dementia intersect in the hippocampal formation." Epilepsia 52 Suppl (1): 39-46. - 108.
Nohl H. Hegner D. et al. 1979 Responses of mitochondrial superoxide dismutase, catalase and glutathione peroxidase activities to aging." Mech Ageing Dev11 3 145 51 - 109.
Novoselov S. V. Kryukov G. V. et al. 2007 Selenoprotein H is a nucleolar thioredoxin-like protein with a unique expression pattern." Journal of Biological Chemistry282 16 11960 8 - 110.
Pages N. Maurois P. et al. 2010 Activities of alpha-asarone in various animal seizure models and in biochemical assays might be essentially accounted for by antioxidant properties." Neurosci Res68 4 337 44 - 111.
Palop J. J. Mucke L. 2009 Epilepsy and cognitive impairments in Alzheimer disease." Arch Neurol66 4 435 40 - 112.
Panee J. Stoytcheva Z. R. et al. 2007 Selenoprotein H is redox-sensing high mobility group family DNA-binding protein that up-regulates genes involved in glutathione synthesis and phase II detoxification." Journal of Biological Chemistry282 33 23759 23765 - 113.
Papp L. V. Lu J. et al. 2007 From selenium to selenoproteins: synthesis, identity, and their role in human health." Antioxid Redox Signal9 7 775 806 - 114.
Poduri A. Lowenstein D. 2011 Epilepsy genetics-past, present, and future." Curr Opin Genet Dev21 3 325 32 - 115.
Prunetti P. Perucca E. 2011 New and forthcoming anti-epileptic drugs." Curr Opin Neurol24 2 159 64 - 116.
Puzanowska-Tarasiewicz H. Kuzmicka L. et al. 2009 Biological function of some elements and their compounds. II. Selenium, selenate, selenium organic compounds." Pol Merkur Lekarski27 159 249 52 - 117.
Ramaekers V. T. Calomme N. et al. 1994 Selenium Deficiency Triggering Intractable Seizures." Neuropediatrics25 4 217 223 - 118.
Ran Q. Liang H. et al. 2007 Reduction in glutathione peroxidase 4 increases life span through increased sensitivity to apoptosis." J Gerontol A Biol Sci Med Sci62 9 932 42 - 119.
Rao S. C. Dove G. et al. 2009 Recurrent seizures in patients with dementia: frequency, seizure types, and treatment outcome." Epilepsy Behav14 1 118 20 - 120.
Rees M. I. 2010 The genetics of epilepsy--the past, the present and future." Seizure19 10 680 3 - 121.
Reeves M. A. Bellinger F. P. et al. 2010 The neuroprotective functions of selenoprotein M and its role in cytosolic calcium regulation." Antioxid Redox Signal12 7 809 18 - 122.
Renko K. Hofmann P. J. et al. 2009 Down-regulation of the hepatic selenoprotein biosynthesis machinery impairs selenium metabolism during the acute phase response in mice." Faseb Journal23 6 1758 1765 - 123.
Rotruck J. T. Pope A. L. et al. 1973 Selenium: biochemical role as a component of glutathione peroxidase." Science179 73 588 90 - 124.
Rubin J. J. Willmore L. J. 1980 Prevention of Iron-Induced Epileptiform Discharges in Rats by Treatment with Anti-Peroxidants." Experimental Neurology67 3 472 480 - 125.
Saito Y. Hayashi T. et al. 1999 Selenoprotein P in human plasma as an extracellular phospholipid hydroperoxide glutathione peroxidase. Isolation and enzymatic characterization of human selenoprotein p." Journal of Biological Chemistry274 5 2866 71 - 126.
Sander J. W. A. S. 1993 Some Aspects of Prognosis in the Epilepsies- a Review." Epilepsia34 6 1007 1016 - 127.
Santamaria A. Vazquez-Roman B. et al. 2005 Selenium reduces the proapoptotic signaling associated to NF-kappaB pathway and stimulates glutathione peroxidase activity during excitotoxic damage produced by quinolinate in rat corpus striatum." Synapse58 4 258 66 - 128.
Savaskan N. E. Brauer A. U. et al. 2003 Selenium deficiency increases susceptibility to glutamate-induced excitotoxicity." Faseb Journal17 1 112 4 - 129.
Scarmeas N. Honig L. S. et al. 2009 Seizures in Alzheimer disease: who, when, and how common?" Arch Neurol66 8 992 7 - 130.
Schomburg L. Schweizer U. et al. 2003 Gene disruption discloses role of selenoprotein P in selenium delivery to target tissues." Biochem J 370(Pt 2): 397-402. - 131.
Schwarz K. Porter L. A. et al. 1972 Some regularities in the structure-function relationship of organoselenium compounds effective against dietary liver necrosis." Ann N Y Acad Sci19 2 200 14 - 132.
Schwarz K. Stesney J. A. et al. 1959 Relation between selenium traces in L-cystine and protection against dietary liver necrosis." Metabolism8 1 88 90 - 133.
Schweizer U. Brauer A. U. et al. 2004 Selenium and brain function: a poorly recognized liaison." Brain Res Brain Res Rev45 3 164 78 - 134.
Sharma V. Nehru B. et al. 2010 Antioxidant potential of curcumin against oxidative insult induced by pentylenetetrazol in epileptic rats." Methods Find Exp Clin Pharmacol32 4 227 32 - 135.
Sisodiya S. M. Mefford H. C. 2011 Genetic contribution to common epilepsies." Curr Opin Neurol24 2 140 5 - 136.
Small-Howard A. L. Berry M. J. 2005 Unique features of selenocysteine incorporation function within the context of general eukaryotic translational processes." Biochem Soc Trans 33(Pt 6): 1493-7. - 137.
Sozmen V. Baybas S. et al. 2011 Frequency of epilepsies in family members of patients with different epileptic syndromes." Eur Neurol65 1 4 9 - 138.
Squires J. E. Berry M. J. 2008 Eukaryotic selenoprotein synthesis: mechanistic insight incorporating new factors and new functions for old factors." IUBMB Life60 4 232 5 - 139.
Stadtman T. C. Davis J. N. et al. 1989 Biochemical and genetic analysis of Salmonella typhimurium and Escherichia coli mutants defective in specific incorporation of selenium into formate dehydrogenase and tRNAs." Biofactors2 1 35 44 - 140.
Stefani A. Spadoni F. et al. 1997 Voltage-activated calcium channels: targets of antiepileptic drug therapy?" Epilepsia38 9 959 65 - 141.
Steinert P. Bachner D. et al. 1998 Analysis of the mouse selenoprotein P gene." Biological Chemistry379 6 683 691 - 142.
Steinert T. Baier H. et al. 2011 Epileptic Seizures During Treatment with Antidepressants and Neuroleptics." Fortschr Neurol Psychiatr79 3 138 143 - 143.
Strzelczyk A. Cenusa M. et al. 2011 Management and long-term outcome in patients presenting with ictal asystole or bradycardia." Epilepsia52 6 1160 7 - 144.
Sun Y. Butler J. A. et al. 2001 Glutathione peroxidase activity and selenoprotein W levels in different brain regions of selenium-depleted rats." Journal of Nutritional Biochemistry12 2 88 94 - 145.
Suzuki Y. 2011 Molecular basis of neurogenetic diseases." Brain Dev.doi:10.1016/ j.physletb.2003.10.071 - 146.
Takebe G. Yarimizu J. et al. 2002 A comparative study on the hydroperoxide and thiol specificity of the glutathione peroxidase family and selenoprotein P." Journal of Biological Chemistry277 43 41254 8 - 147.
Tamura T. Stadtman T. C. 2002 Mammalian thioredoxin reductases." Methods Enzymol347 297 306 - 148.
Tome Ada. R. Ferreira P. M. et al. 2010 Inhibitory action of antioxidants (ascorbic acid or alpha-tocopherol) on seizures and brain damage induced by pilocarpine in rats." Arq Neuropsiquiatr68 3 355 61 - 149.
Tsai J. J. 2005 Mortality of epilepsy from national vital statistics and University epilepsy clinic in Taiwan." Epilepsia 46 Suppl1 1 8 10 - 150.
Tujebajeva R. M. Copeland P. R. et al. 2000 Decoding apparatus for eukaryotic selenocysteine insertion." EMBO Rep1 2 158 63 - 151.
Urbach H. 2005 Imaging of the epilepsies." Eur Radiol15 3 494 500 - 152.
Vendeland S. C. Beilstein M. A. et al. 1993 Purification and properties of selenoprotein W from rat muscle." Journal of Biological Chemistry268 23 17103 7 - 153.
Verrotti A. Loiacono G. et al. 2011 Pharmacotherapy for children and adolescents with epilepsy." Expert Opin Pharmacother12 2 175 94 - 154.
Vezzani A. French J. et al. 2011 The role of inflammation in epilepsy." Nat Rev Neurol7 1 31 40 - 155.
Wang G. S. Geng D. Q. et al. 2010 Protective effect of Na2SeO3 against cerebral ischemia-reperfusion injury to the hippocampal neurons in rats." Nan Fang Yi Ke Da Xue Xue Bao30 10 2336 9 - 156.
Weber G. F. Maertens P. et al. 1991 Glutathione peroxidase deficiency and childhood seizures." Lancet337 8755 1443 4 - 157.
Westmark C. J. Westmark P. R. et al. 2010 Alzheimer’s disease and Down syndrome rodent models exhibit audiogenic seizures." J Alzheimers Dis20 4 1009 13 - 158.
Whanger P. D. 2009 Selenoprotein expression and function-selenoprotein W." Biochim Biophys Acta1790 11 1448 52 - 159.
Wilke C. Worrell G. et al. 2011 Graph analysis of epileptogenic networks in human partial epilepsy." Epilepsia52 1 84 93 - 160.
Willmore L. J. Rubin J. J. 1981 Antiperoxidant pretreatment and iron-induced epileptiform discharges in the rat: EEG and histopathologic studies." Neurology31 1 63 9 - 161.
Wirth E. K. Conrad M. et al. 2010 Neuronal selenoprotein expression is required for interneuron development and prevents seizures and neurodegeneration." FASEB J24 3 844 52 - 162.
Wu M. Kang M. M. et al. 2010 Selenium compounds activate early barriers of tumorigenesis." Journal of Biological Chemistry285 16 12055 62 - 163.
Xiong S. Markesbery W. R. et al. 2007 Seleno-L-methionine protects against beta-amyloid and iron/hydrogen peroxide-mediated neuron death." Antioxid Redox Signal9 4 457 67 - 164.
Xu X. M. Carlson B. A. et al. 2007 New developments in selenium biochemistry: selenocysteine biosynthesis in eukaryotes and archaea." Biol Trace Elem Res119 3 234 41 - 165.
Yang G. Q. Xia Y. M. 1995 Studies on human dietary requirements and safe range of dietary intakes of selenium in China and their application in the prevention of related endemic diseases." Biomed Environ Sci8 3 187 201 - 166.
Yang X. E. Chen W. R. et al. 2007 Improving human micronutrient nutrition through biofortification in the soil-plant system: China as a case study." Environ Geochem Health29 5 413 28 - 167.
Yasuda S. Sugiura H. et al. 2011 38 Map Kinase Inhibitors as Potential Therapeutic Drugs for Neural Diseases." Cent Nerv Syst Agents Med Chem 11(1): 45-59. - 168.
Yuzbasioglu A. Karatas H. et al. 2009 Changes in the expression of selenoproteins in mesial temporal lobe epilepsy patients." Cell Mol Neurobiol29 8 1223 31 - 169.
Zafar K. S. Siddiqui A. et al. 2003 Dose-dependent protective effect of selenium in rat model of Parkinson’s disease: neurobehavioral and neurochemical evidences." Journal of Neurochemistry84 3 438 446 - 170.
Zhang S. Rocourt C. et al. 2010 Selenoproteins and the aging brain." Mech Ageing Dev131 4 253 60 - 171.
Zhang Y. Zhou Y. et al. 2008 Comparative analysis of selenocysteine machinery and selenoproteome gene expression in mouse brain identifies neurons as key functional sites of selenium in mammals." Journal of Biological Chemistry283 4 2427 2438