Marta Kowalska

By Michał Prendecki, Jolanta Florczak-Wyspianska, Marta Kowalska, Margarita Lianeri, Wojciech Kozubski and Jolanta Dorszewska

Normal aging begins after 60 years of age. According to Harman, the accumulation of free radicals, which results from weakening of repair and protective mechanisms, takes place in the aging brain. It is believed that especially in the population of the most elderly there is increased incidence of both dementia and depression. The causes of these central nervous system disorders in the aging human body are changes at the molecular level, such as changes in the biochemical parameters, the accumulation of mutations in nuclear and mitochondrial DNA, and epigenetic changes. Biomarkers associated with aging of the brain include accumulated deposits of β-amyloid (Aβ), disturbed cholesterol homeostasis, altered neuroimaging parameters, and impaired glucose metabolism. Genetic factors are also responsible for normal aging, for example, SIRT1, AKT1, and CDKN1A, and among them the longevity genes, such as FOXO3A and CETP. Dementia as well as cognitive decline may be modified by poly-T variants of TOMM40 and APOE alleles via influencing the level of apolipoprotein E (apoE) in the brain and in the plasma as well as by its ability of Aβ clearance.

Part of the book: Update on Dementia

By Jolanta Dorszewska, Urszula Lagan-Jedrzejczyk, Marta Kowalska, Katarzyna Wize and Wojciech Kozubski

Epilepsy is one of the most common neurological diseases, affecting approximately 1% of the population. It is a chronic disease and increased incidence falls in the period up to 1 year and 65 years of age. Most patients require long-term antiepileptic drugs (AEDs) therapy. In addition, approximately 30% of patients with epilepsy do not obtain satisfactory seizure control, which is defined as drug-resistant epilepsy. It is postulated that one of the causes of drug resistance can be polymorphisms of ABCB1/MDR1 gene, tested particularly in tumors. It is believed that the old generation of AEDs, e.g. CBZ, VPA, may change plasma Hcy, asymmetric dimethylarginine (ADMA) levels, disturb lipid levels, C-reactive protein, vitamins, markers of oxidative stress, which are risk factors for vascular and neurodegenerative diseases. Changes in the level of risk factors for vascular disease caused by enzymes inducing AEDs, CBZ, PB, and PHT lead to a small increase in the risk of myocardial infarction. Alteration of Hcy and ADMA levels are also linked to genetic factors, e.g. genetic variants of MTHFR, MTR, MTHFD1, CBS, DDAH1, eNOS genes. Individualization of treatment with AEDs and prevention against cardiovascular disease in patients with epilepsy may bring the best therapeutic effects in these patients.

Part of the book: Epileptology

By Jolanta Dorszewska, Jolanta Florczak-Wyspianska, Marta Kowalska, Marcin Stanski, Alicja Kowalewska and Wojciech Kozubski

Serotonin (5-HT) is responsible for anxiety, aggression, and stress. Alterations in a serotonergic system play a significant role in pathogenesis of neurological diseases and neuropsychiatric disorders. A wide range of disturbances associated with serotonergic neurotransmission results from different functions of 5-HT in a nervous system. It is believed that 5-HT may be involved in the pathogenesis of migraine, epilepsy, Parkinson’s disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), attention-deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD). In these diseases, disturbances of 5-HT and its metabolites, such as 5-hydroxyindoleacetic acid (5-HIAA), were observed in the plasma, blood platelets, and cerebrospinal fluid (CSF). Changes in the level of this biogenic amine (5-HT) may be associated with malfunction of 5-HT receptors, reuptake transporter for 5-HT (5-HTT, SERT), the enzymes responsible for the synthesis and metabolism of 5-HT, and genetic variants for serotonergic system. It seems that 5-HT and its metabolites may be used as a diagnostic and prognostic marker for neurological diseases or a target for more efficient therapy in neurology in the future.

Part of the book: Serotonin

By Marta Kowalska, Michal Owecki, Michal Prendecki, Katarzyna Wize, Joanna Nowakowska, Wojciech Kozubski, Margarita Lianeri and Jolanta Dorszewska

Current knowledge indicates that the aging process starts with subclinical changes at the molecular level. These include the accumulation of mutations, telomere attrition, and epigenetic alterations leading to genomic instability. Such defects multiply exponentially over time, resembling a “snowball effect,” and eventually leading to morphological and functional deterioration of the brain, including progressive neuronal loss, reduced levels of neurotransmitters, excessive inflammation, and disrupted integrity of vessels, followed by infarction and microbleeds. Additionally, the decreasing efficiency of DNA repair mechanisms increases the susceptibility to reactive oxygen species and spontaneous mutagenesis, resulting in age-related neoplasia. Moreover, the malnutrition and malabsorption seen commonly in the elderly may cause deficiency of vitamin B12 and folic acid, both necessary for homocysteine metabolism, and lead to vascular damage. Altogether, these lead to brain damage in old age and greatly increase the risk of developing diseases of the central nervous system, such as stroke, epilepsy, Parkinson’s disease, Alzheimer’s disease, and other dementias.

Part of the book: Senescence