EFFECTS OF PRENATAL STRESS ON EARLY POSTNATAL DEVELOPMENT OF GLUTAMATERGIC NEURONS IN THE MOUSE BRAIN

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We studied the effects of prenatal stress on early postnatal development of the brain in mouse pups (PS) whose dams had been exposed daily to restraint stress during pregnancy (gestational days 14-18), with special reference to the expression of corticotropin-releasing factor (CRH), vesicular glutamate transporters (VGLUT1 and VGLUT2), and a synaptic vesicle marker protein (SV2). In a comparison with age-matched control pups born of unstressed dams, in situ hybridization analysis revealed a statistically significant reduction of CRH gene expression in the hypothalamic paraventricular nucleus of the PS pups at postnatal days 10 (P10), suggesting a functional alteration in the core neuroendocrine circuit of the stress response mechanism. Immunohistochemical analysis of the medial habenular nucleus followed by semi-quantitative evaluation revealed that VGLUT1 staining, but not VGLUT2 staining, is markedly reduced in the P10 PS pups compared to controls of the same age, and that such a difference between PS and control pups becomes undetectable at P21. These findings suggest that the embryonic environment, at least during late pregnancy, alters the activity of the neuroendocrine system involved in the stress response and influences the early postnatal development of glutamatergic neurons in a particular brain region.