title: Biochemical, histopathological and morphological profiling of a rat model of early immune stimulation: relation to psychopathology.
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.
authors.affiliation: Prague Psychiatric Center, Prague, Czech Republic; National Institute of Mental Health, Klecany, Czech Republic; Third Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Anna
authors.initials: A
authors.lastname: Kubesova
authors.affiliation: Prague Psychiatric Center, Prague, Czech Republic; National Institute of Mental Health, Klecany, Czech Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Tejkalova
authors.affiliation: Institute of Chemical Technology, Prague, Czech Republic.
authors.forename: Kamila
authors.initials: K
authors.lastname: Syslova
authors.affiliation: Institute of Chemical Technology, Prague, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Kacer
authors.affiliation: Institute of Chemical Technology, Prague, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Vondrousova
authors.affiliation: Prague Psychiatric Center, Prague, Czech Republic; National Institute of Mental Health, Klecany, Czech Republic; Third Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Filip
authors.initials: F
authors.lastname: Tyls
authors.affiliation: Prague Psychiatric Center, Prague, Czech Republic; National Institute of Mental Health, Klecany, Czech Republic; Third Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Michaela
authors.initials: M
authors.lastname: Fujakova
authors.affiliation: Prague Psychiatric Center, Prague, Czech Republic; National Institute of Mental Health, Klecany, Czech Republic; Third Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Palenicek
authors.affiliation: Prague Psychiatric Center, Prague, Czech Republic; National Institute of Mental Health, Klecany, Czech Republic; Third Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Horacek
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D015306:Biogenic Monoamines / Q000097:blood / Q000378:metabolism; D001835:Body Weight; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D007737:Kynurenine / Q000378:metabolism; D008297:Male; D001523:Mental Disorders / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology / Q000523:psychology; D053858:Metabolic Networks and Pathways; D055442:Metabolome; D017628:Microglia / Q000378:metabolism; D015213:Neuroimmunomodulation; D018377:Neurotransmitter Agents / Q000378:metabolism; D011599:Psychopathology; D051381:Rats; D014364:Tryptophan / Q000378:metabolism
chemical_list: D015306:Biogenic Monoamines; D018377:Neurotransmitter Agents; D007737:Kynurenine; D014364:Tryptophan