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  • Blackwell Science Ltd  (3)
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  • 1
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The dentate gyrus is one of the few areas of the adult brain that continues to produce neurons and to express the embryonic polysialylated isoforms of neuronal cell adhesion molecules (PSA-NCAM). The stress hormone corticosterone exerts a complex modulation on neurogenesis and PSA-NCAM, and previous studies have shown that mature granule cells require corticosterone for their survival. Thus, the aim of our work was to investigate the respective role of the different corticosteroid receptors on these three parameters in adrenalectomized rats. It was found that treatment with a low dose of the mineralocorticoid receptor agonist, aldosterone, prevents only the adrenalectomy-induced increase in cell death. Treatment with a higher dose of aldosterone normalized cell proliferation whereas PSA-NCAM expression was normalized only by treatment with the glucocorticoid receptor agonist, RU 28362. It is concluded that stimulation of the mineralocorticoid receptor is sufficient to mediate the effects of corticosterone on neurogenesis and to protect mature cells from cell death whereas stimulation of the glucocorticoid receptor is necessary to modulate PSA-NCAM expression.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Ageing is accompanied by a decline in neurogenesis and in polysialylated isoforms of neural cell adhesion molecule (PSA-NCAM) expression within the hippocampus and by elevated basal levels of circulating corticosterone. In a companion study, we demonstrated that suppression of corticosterone by adrenalectomy increased neurogenesis and PSA-NCAM expression in the dentate gyrus of adult rats. Here we show that adrenalectomy increased neurogenesis in this structure in old rats, as measured by the incorporation of 5-bromo-2′-deoxyuridine in neuronal progenitors. This effect was prevented by corticosterone replacement. In contrast, PSA-NCAM expression remained unchanged in comparison with controls. Thus, in the aged brain, stem cells are still present and able to enter the cell cycle. This may point to ways of protecting or treating age-related cognitive impairments.
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  • 3
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The hippocampal formation is one of the brain areas where neurogenesis persists during adulthood, with new neurons being continuously added to the population of dentate granule cells. However, the functional implications of this neurogenesis are unknown. On the other hand, the hippocampal formation is particularly concerned with the detection of novelty, and there are indications that dentate granule cells play a significant role in this function. Recently, the existence of inter-individual differences in behavioural reactivity to novelty has been evidenced, related to differences in the reactivity of the hypothalamic–pituitary–adrenal axis (HPA). Rats that are highly reactive to novelty (HR) exhibit a prolonged corticosterone secretion in response to novelty and to stress when compared with low reactive rats (LR). Taking advantage of the existence of these inter-individual differences, we investigated whether neurogenesis in the dentate gyrus is correlated with the behavioural trait of reactivity to novelty. Rats were first selected according to their locomotor reactivity to a novel environment. Two weeks later, cell proliferation, evaluated by the incorporation of 5-bromo-2′-deoxyuridine (BrdU) in progenitors, was studied by immunohistochemistry. We found that cell proliferation in the dentate gyrus was negatively correlated with locomotor reactivity to novelty. Indeed, cell proliferation in LR rats was twice that observed in HR rats. In contrast, survival of nascent neurons was not influenced by the behavioural trait of reactivity to novelty. Using an unbiased stereology, we show that LR rats had more cells within the granule cell layer of the dentate gyrus than did HR rats. These results demonstrate the existence of inter-individual differences in neurogenesis and total granule cell number within the dentate gyrus. These differences in hippocampal plasticity can be predicted by the behavioural trait of reactivity to novelty.
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