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Immunohistochemical Analysis in the Rat Central Nervous System and Peripheral Lymph Node Tissue Sections
Published on: November 14, 2016
Biochemical, histopathological and morphological profiling of a rat model of early immune stimulation: relation to
Anna Kubesova1, Hana Tejkalova2, Kamila Syslova3
1Prague Psychiatric Center, Prague, Czech Republic; National Institute of Mental Health, Klecany, Czech Republic; Third Faculty of Medicine, Charles University, Prague, Czech Republic.
Insights
Early life immune challenges in rats alter brain chemistry and structure, impacting neurotransmitters and leading to neuroinflammation and reduced dopamine synthesis, relevant to human brain disorders.
Area of Science:
- Neuroscience
- Immunology
- Psychiatry
Background:
- Perinatal immune challenges are linked to neurodevelopmental dysfunction and immune dysregulation.
- These effects show translational validity to human neuropsychiatric disorders like schizophrenia, mood disorders, autism, Parkinson's, and Alzheimer's disease.
Purpose of the Study:
- To investigate the impact of early immune stimulation via postnatal lipopolysaccharide administration on neurobiology.
- To elucidate biochemical, histopathological, and morphological changes relevant to human psychopathology.
Main Methods:
- Adult male Wistar rats were subjected to systemic postnatal lipopolysaccharide administration.
- Examined brain and plasma levels of monoamines, neurotransmitters (glutamate, GABA), and tryptophan metabolites (kynurenine pathway).
- Assessed glial cell activation, neurodegeneration, hippocampal volume, and dopaminergic synthesis (tyrosine hydroxylase) in the substantia nigra.
Main Results:
- Early immune stimulation altered neurotransmitter and metabolite levels in adult rats.
- Activated the kynurenine pathway of tryptophan metabolism.
- Induced astrogliosis, reduced hippocampal volume, and decreased tyrosine hydroxylase immunoreactivity in the substantia nigra.
Conclusions:
- Early life immune stimulation significantly impacts brain biochemistry, histopathology, and morphology.
- These changes provide a neurobiological basis for the link between early immune challenges and neuropsychiatric disorders.
- Findings support the pathophysiological role of early immune stimulation in conditions like schizophrenia and neurodegenerative diseases.
Abstract:
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.
