Biochemical, Histopathological and Morphological Profiling of a Rat Model of Early Immune Stimulation: Relation to Psychopathology
| Autor: | A. Kubesova, Jana Vondroušová, Petr Kačer, M. Fujakova, Kamila Syslová, Hana Tejkalová, Tomáš Páleníček, Jiri Horacek, Filip Tylš |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
medicine.medical_specialty Pathology Kynurenine pathway Neuroimmunomodulation lcsh:Medicine Substantia nigra medicine.disease_cause chemistry.chemical_compound Dopamine Internal medicine medicine Animals Biogenic Monoamines lcsh:Science Kynurenine Neurotransmitter Agents Multidisciplinary Tyrosine hydroxylase Psychopathology business.industry Mental Disorders Dopaminergic lcsh:R Body Weight Tryptophan Brain Immune dysregulation Rats Disease Models Animal Monoamine neurotransmitter Endocrinology chemistry Astrocytes Metabolome lcsh:Q Microglia business Metabolic Networks and Pathways medicine.drug Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 10, Iss 1, p e0115439 (2015) |
| ISSN: | 1932-6203 |
| Popis: | Perinatal immune challenge leads to neurodevelopmental dysfunction, permanent immune dysregulation and abnormal behaviour, which have been shown to have translational validity to findings in human neuropsychiatric disorders (e.g. schizophrenia, mood and anxiety disorders, autism, Parkinson’s disease and Alzheimer’s disease). The aim of this animal study was to elucidate the influence of early immune stimulation triggered by systemic postnatal lipopolysaccharide administration on biochemical, histopathological and morphological measures, which may be relevant to the neurobiology of human psychopathology. In the present study of adult male Wistar rats we examined the brain and plasma levels of monoamines (dopamine, serotonin), their metabolites, the levels of the main excitatory and inhibitory neurotransmitters glutamate and γ-aminobutyric acid and the levels of tryptophan and its metabolites from the kynurenine catabolic pathway. Further, we focused on histopathological and morphological markers related to pathogenesis of brain diseases - glial cell activation, neurodegeneration, hippocampal volume reduction and dopaminergic synthesis in the substantia nigra. Our results show that early immune stimulation in adult animals alters the levels of neurotransmitters and their metabolites, activates the kynurenine pathway of tryptophan metabolism and leads to astrogliosis, hippocampal volume reduction and a decrease of tyrosine hydroxylase immunoreactivity in the substantia nigra. These findings support the crucial pathophysiological role of early immune stimulation in the above mentioned neuropsychiatric disorders. |
| Databáze: | OpenAIRE |
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