Depression: reduced number of granule cells in the hippocampus of female, but not male, rats due to prenatal restraint stress

Abstract

It has been hypothesized that decreased neurogenesis in the dentate gyrus may be involved in mediating depressive disorders, which are 1.5-3 times more frequent in women than in men. Additionally, prenatal stress may increase the risk of developing depression in adulthood. However, the interrelations between prenatal stress and the development of depression in adulthood, preferentially in females, are not understood. Here, we subjected pregnant rats to a single 20-min period of restraint stress on day 18 after mating. When the offspring were 75 days of age, the numbers of granule cells and pyramidal cells (area CA1-3) in the hippocampus were analyzed with the optical fractionator. The Cavalieri's principle was applied to analyze the volumes of both granule cell layer and pyramidal cell layer in the hippocampus. Prenatally stressed females, but not males, had reduced numbers of hippocampal granule cells compared to their non-prenatally stressed counterparts. This is the first report of a sex-specific difference concerning the reduction of the number of hippocampal granule cells due to prenatal stress. In humans, prenatal stress may induce cell loss in the granule cells of the hippocampus preferentially in females compared to males, and this may be a sex-specific predisposing factor for the development of depression in adulthood.

Treatment with an SSRI antidepressant restores hippocampo-hypothalamic corticosteroid feedback and reverses insulin resistance in low-birth-weight rats

“…Since chronic stress has been proposed to cause atrophy of the hippocampus, we also measured hippocampal mRNA expression patterns of two proteins involved in cellular apoptosis (i.e., Bax and Bcl-2), but we did not find any changes. Structural hippocampal change following a restraint prenatal stress paradigm has been observed, but only in females (62). Whether this is relevant in the context of the present work awaits future studies.…”

Adult female wildtype, but not oestrogen receptor β knockout, mice have decreased depression-like behaviour during pro-oestrus and following administration of oestradiol or diarylpropionitrile

“…For example, females may be particularly sensitive to the effects of stress. As one example, gestational stress produces greater loss in hippocampal cells among females compared with their male rat counterparts (Schmitz, et al, 2002). Another consideration to make is that, in addition to the role of the HPA, HPG steroids produce robust effects on affective behaviour of rodents, which may mask the role of sex differences for these behaviours.…”

Original article Prenatal exposure of diclofenac sodium affects morphology but not axon number of the median nerve of rats

“…Prenatal exposure of diclofenac sodium affects morphology but not axon number of the median nerve of rats adulthood [22]. DS may show its neurotoxic effects through not only growth inhibition but also differentiation inhibition.…”