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.

The effect of tacrine (THA), the cholinesterase inhibitor, and Ginkgo biloba extract (EGb) on the sodium-dependent high-affinity choline uptake (HACU) into hippocampal synaptosomes was studies in vivo in model experiments after long-term administration in old rats (THA 5 or 10 mg/kg/day p.o. for 3 months; EGb 50 or 100 mg/kg/day p.o. for 30 days) and in vitro tests. EGb increased HACU both in vivo and in vitro experiments. On the contrary, THA induced a decrease of HACU under both conditions, suggesting a negative impact on the cholinergic neuronal activity.

adequate psychosocial support, and better coordination between infectious-diseases and substance-use clinic teams.

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