Abstract
Toxoplasma gondii (T. gondii) causes toxoplasmic encephalitis resulting from reactivation of latent toxoplasmosis. It is the most frequent clinical manifestation, characterized by multiple necrotizing brain lesions. Bradyzoite tissue cysts activate an immune response that has a major impact on controlling parasite persistence in the brain. The immune mechanisms stimulated in the brain cause a local inflammatory mediated by Th1 immune reaction cytokines. Several studies have linked this process to that active during different neuropsychiatric disorders, such as Schizophrenia. In addition to the immune reaction activated in the brain, this latter has the capacity to stimulate neurotransmitter production. T. gondii induces high concentrations of dopamine and tyrosine hydroxylase in the central nervous system and has also been shown to increase kynurenine/tryptophan ratio and elevated Kynurenic acid level, mainly in astrocyte cells. This imbalance plays a role in the pathophysiology of Schizophrenia. Results of different studies explain in this chapter support the idea that Toxoplasma is an etiological factor in Schizophrenia.
Keywords
- Toxoplasma gondii
- neuropsychiatric disorders
- schizophrenia
- immunity
- neurotransmitter
1. Introduction
Toxoplasmosis is one of the most common parasitic zoonosis in the world. Its causative agent,
2. The cerebral anti-Toxoplasma immune reaction
2.1 The central nervous system immunity
The central nervous system is closely linked to the immune system at several levels. The cerebral parenchyma is separated from the periphery by the BBB, the integrity of which is maintained by tight endothelial junctions. This barrier under normal conditions prevents the entry of mediators such as activated leukocytes, antibodies, complement factors, and cytokines. The myeloid cell line plays a crucial role in the development of immune responses at the central level, it includes two main subtypes: microglial cells, distributed in the cerebral parenchyma; perivascular macrophages located in the capillaries of the basal lamina brain and the choroid plexus. In addition, astrocytes, oligodendrocytes, endothelial cells, and neurons are also involved in the immune response in the CNS. By modulating synaptogenesis, microglial cells are more particularly involved in the restoration of neuronal connectivity following inflammation. These cells release immune mediators, such as cytokines, that modulate synaptic transmission and alter the morphology of dendritic spines during the inflammatory process after injury. Thus, the expression and release of immune mediators in the cerebral parenchyma are closely related to the plastic morphophysiological changes in the dendritic spines of neurons. Based on these data, it has been proposed that these immune mediators are also involved in the learning and memory processes. Microvasculature is a key element of brain damage. Endothelial cells are an important source of immune mediators such as a nitric oxide (NO), which are involved in the process of immune cell adhesion [12, 13]. A recent study shows that
2.2 The mechanism of T. gondii invasion in the brain
In the brain, dendritic cells and monocytes are the most permissive cells for initial
The transepithelial migration capacity of tachyzoites is implicated in the passage of the parasite across the BBB. This could be done through the interaction of the intercellular adhesion molecule 1 (ICAM-1) of the BBB cells with the parasite MIC2 protein [20]. This interaction is important for transmigration of tachyzoites, as demonstrated
Macrophages are also responsible for the spread of
2.3 The regulation of the cerebral immune mechanism during T. gondii infection
After
3. The role of T. gondii in the etiopathogenetic of psychiatric diseases
Any infectious agent can affect neurons and brain structures after activation of the proinflammatory immune response and neurotransmitters, thus causing psychosis. Among the different infectious agents,
A bunch of data hypothesizes that latent toxoplasmosis may be a risk factor for the depression. The low-grade inflammation caused by the chronic
3.1 The cerebral immune response activated during schizophrenia and T. gondii infection
In cerebral toxoplasmosis, the balance between host immunity and defense mechanisms in the event of parasite escape is the basis of asymptomatic infection. Inflammation and immune deregulation have consistently been observed in both
3.2 The neurobiological studies related to T. gondii infection to schizophrenia disease
There are differences in
The most likely mechanism of action in Schizophrenia affects neurotransmission in specific brain areas such as the thalamic-cortical limbic circuit of DOPA, 5-hydroxytryptamine (5-HT), gamma-aminobutyric acid (GABA), and glutamate. As a result, schizophrenic patients show abnormal levels of these neurotransmitters. Studies show an increase in DOPA release in the limbic system [47, 66]. In addition,
In addition to DOPA, studies have also evaluated alterations of the kynurenine pathway (KYN) and involvement of TRP [71, 72]. In immunocompetent hosts, infection with
4. Conclusion
The question that
Conflict of interest
The authors declare that there are no conflicts of interest regarding the publication of this chapter.
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