Despite higher glucocorticoid levels and stress responses in female rats, both sexes exhibit similar stress-induced changes in hippocampal neurogenesis.

Sex differences in stress reactivity may be one of the factors underlying the increased sensitivity for the development of psychopathologies in women. Particularly, an increased hypothalamic-pituitary-adrenal (HPA) axis reactivity in females may exacerbate stress-induced changes in neuronal plasticity and neurogenesis, which in turn may contribute to an increased sensitivity to psychopathology. The main aim of the present study was to examine male-female differences in stress-induced changes in different aspects of hippocampal neurogenesis, i.e. cell proliferation, differentiation and survival. Both sexes were exposed to a wide variety of stressors, where after differences in HPA-axis reactivity and neurogenesis were assessed. To study the role of oestradiol in potential sex differences, ovariectomized females received low or high physiological oestradiol level replacement pellets. The results show that females in general have a higher basal and stress-induced HPA-axis activity than males, with minimal differences between the two female groups. Cell proliferation in the dorsal hippocampus was significantly higher in high oestradiol females compared to low oestradiol females and males, while doublecortin (DCX) expression as a marker of cell differentiation was significantly higher in males compared to females, independent of oestradiol level. Stress exposure did not significantly influence cell proliferation or survival of new cells, but did reduce DCX expression. In conclusion, despite the male-female differences in HPA-axis activity, the effect of repeated stress exposure on hippocampal cell differentiation was not significantly different between sexes.

Chronic partial sleep deprivation reduces brain sensitivity to glutamate N-methyl-D-aspartate receptor-mediated neurotoxicity.

It has been hypothesized that insufficient sleep may compromise neuronal function and contribute to neurodegenerative processes. While sleep loss by itself may not lead to cell death directly, it may affect the sensitivity to a subsequent neurodegenerative insult. Here we examined the effects of chronic sleep restriction (SR) on the vulnerability of the brain to N-methyl-d-aspartate (NMDA)-induced excitotoxicity. Animals were kept awake 20 h per day and were only allowed to rest during the first 4 h of the light phase, i.e. their normal circadian resting phase. After 30 days of SR all rats received a unilateral injection with a neurotoxic dose of NMDA into the nucleus basalis magnocellularis (NBM). Brains were collected for assessment of damage. In the intact non-injected hemisphere, the number of cholinergic cells in the NBM and the density of their projections in the cortex were not affected by SR. In the injected hemisphere, NMDA caused a significant loss of cholinergic NBM cells and cortical fibres in all animals. However, the loss of cholinergic cells was attenuated in the SR group as compared with the controls. These data suggest that, if anything, SR reduces the sensitivity to a subsequent excitotoxic insult. Chronic SR may constitute a mild threat to the brain that does not lead to neurodegeneration by itself but prepares the brain for subsequent neurotoxic challenges. These results do not support the hypothesis that sleep loss increases the sensitivity to neurodegenerative processes.

Maternal separation decreases adult hippocampal cell proliferation and impairs cognitive performance but has little effect on stress sensitivity and anxiety in adult Wistar rats.

Stressful events during childhood are thought to increase the risk for the development of adult psychopathology. A widely used animal model for early life stress is maternal separation (MS), which is thought to affect development and cause alterations in neuroendocrine stress reactivity and emotionality lasting into adulthood. However, results obtained with this paradigm are inconsistent. Here we investigated whether this variation may be related to the type of stressor or the tests used to assess adult stress sensitivity and behavioral performance. Rat pups were exposed to a 3h daily MS protocol during postnatal weeks 1-2. In adulthood, animals were subjected to a wide variety of stressors and tests to obtain a better view on the effects of MS on adult hypothalamic-pituitary-adrenal (HPA) axis regulation, anxiety-like behavior, social interaction and cognition. Also, the influence of MS on adult hippocampal neurogenesis was studied because it might underlie changes in neuroendocrine regulation and behavioral performance. The results show that, independent of the nature of the stressor, MS did not affect the neuroendocrine response. MS did not influence anxiety-like behavior, explorative behavior and social interaction, but did affect cognitive function in an object recognition task. The amount of new born cells in the hippocampal dentate gyrus was significantly decreased in MS animals; yet, cell differentiation and survival were not altered. In conclusion, while interfering with the mother-infant relationship early in life did affect some aspects of adult neuroplasticity and cognitive function, it did not lead to permanent changes in stress sensitivity and emotionality.