Neuroscience
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The nervous system synthesizes steroids that regulate the development and function of neurons and glia, and have neuroprotective properties. The first step in steroidogenesis involves the delivery of free cholesterol to the inner mitochondrial membrane where it can be converted into pregnenolone by the enzyme cytochrome P450side chain cleavage. The peripheral-type benzodiazepine receptor and the steroidogenic acute regulatory protein are involved in this process and appear to function in a coordinated manner. ⋯ The steroidogenic acute regulatory protein gene may be under the control of diverse mechanisms in different neural cell types, since its expression is upregulated by cyclic AMP (cAMP) in gliomas and astrocytes in culture and downregulated by cyclic AMP (cAMP) in Schwann cells. In addition, activation of N-methyl-D-aspartate receptors, and the consequent rise in intracellular calcium levels, activates steroidogenic acute regulatory protein and steroidogenesis in hippocampal neurons. In conclusion, steroidogenic acute regulatory protein is regulated in the nervous system by different physiological and pathological conditions and may play an important role during brain development, aging and after injury.
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The large majority of women receiving hormone therapy initiate therapy early in life for the treatment of menopausal symptoms. However, the Women's Health Initiative Memory Study, the only randomized clinical trial to date on hormone therapy and dementia, was carried out in women age 65 and older. That trial provided important insights into the detrimental effects of hormone therapy on dementia in women initiating later in life. ⋯ To address this important issue, this review focuses on observational trials of hormone therapy and dementia risk, randomized clinical trials of hormone therapy and cognitive function, and basic science studies. These lines of research provide suggestive, but not definitive, evidence that early initiation of hormone therapy may provide cognitive benefits, particularly to verbal memory and other hippocampally mediated functions. Other forms of hormone therapy, other cognitive domains, and cyclic hormone regimens may not conform to this "critical period hypothesis." Further research is needed to test the validity and limits of this hypothesis.
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Different brain rhythms, with both low-frequency and fast-frequency, are grouped within complex wave-sequences. Instead of dissecting various frequency bands of the major oscillations that characterize the brain electrical activity during states of vigilance, it is conceptually more rewarding to analyze their coalescence, which is due to neuronal interactions in corticothalamic systems. This concept of unified brain rhythms does not only include low-frequency sleep oscillations but also fast (beta and gamma) activities that are not exclusively confined to brain-activated states, since they also occur during slow-wave sleep. ⋯ Far from being epiphenomena, spontaneous brain rhythms have an important role in synaptic plasticity. The role of slow-wave sleep oscillation in consolidating memory traces acquired during wakefulness is being explored in both experimental animals and human subjects. Highly synchronized sleep oscillations may develop into seizures that are generated intracortically and lead to inhibition of thalamocortical neurons, via activation of thalamic reticular neurons, which may explain the obliteration of signals from the external world and unconsciousness during some paroxysmal states.
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It is now clear that the study of the effects exerted by steroids on the nervous system may be considered as one of the most interesting and promising topics for biomedical research. Indeed, new effects, mechanisms of action and targets are becoming more and more evident suggesting that steroids are not only important key regulators of nervous system function but they may also represent a new therapeutic tool to combat certain diseases of the nervous system. The present review summarizes recent observations on this topic indicating that while the concept of the nervous system as a target for steroid hormones has been appreciated for decades, a promising new era for the study of these molecules and their actions in the nervous system has been initiated in the last few years.
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Although several randomized controlled trials of surgically menopausal women have provided evidence that estrogen protects aspects of memory, many cross-sectional and longitudinal studies, including those from the Women's Health Initiative Memory Study, have failed to confirm these findings. One critical difference between studies that found a protective effect of estrogen on memory and those that did not is that, in the former studies, treatment with estrogen began at the time of menopause and in the latter studies, it was first administered many years after the menopause had occurred. Recent evidence from rodent, nonhuman primate, and human studies consistently suggests that the timing of the initiation of estrogen treatment with regard to the menopause may be critical to our understanding of the estrogenic effect on memory. Results of these animal and human studies indicate that the initiation of estrogen treatment at the time of menopause, or soon after ovariectomy, provides a window of opportunity for the protection of memory in females whereas the administration of the hormone following a considerable delay in time after ovariectomy or following a natural menopause has little or no beneficial effect on cognition.