Biochemical, Histopathological and Morphological Profiling of a Rat Model of Early Immune Stimulation: Relation to Psychopathology

<div><p>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.</p></div

Brain and plasma levels of glutamate and γ-aminobutyric acid.

<p>Values (ng/ml) represent mean ± SEM.</p><p>Brain and plasma levels of glutamate and γ-aminobutyric acid.</p

Chromatographic separation of the subject analytes.

<p>Chromatographic separation of the subject analytes.</p

Percentage of the area containing Iba1 immunoreactivity.

<p>Values (%) represent mean ± SEM. a) hilus of the dentate gyrus, b) substantia nigra.</p

Brain and plasma levels of monoamines and their metabolites.

<p>Values (ng/ml) represent mean ± SEM.</p><p>Brain and plasma levels of monoamines and their metabolites.</p

Microphotographs of GFAP immunoreactivity in the dentate gyrus (scale bar = 200μm).

<p>a) LPS treated group, b) Control group.</p

Effect of perinatal LPS treatment on hippocampal volume.

<p>Values (mm³) represent mean ± SEM (* indicates p<0.05 from the control group).</p

Percentage of the area containing GFAP immunoreactivity.

<p>Values (%) represent mean ± SEM (* indicates p<0.05 from the control group). a) hilus of the dentate gyrus, b) substantia nigra.</p

Number of TH-positive cells in the substantia nigra, pars compacta.

<p>Values represent mean ± SEM (* indicates p<0.05 from the control group).</p

All datasets compilation

A full compilation of datasets used in the paper in the form of separate txt files for separate analyse