Neuroscience
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11beta-Hydroxysteroid dehydrogenase type 2 is a glucocorticoid metabolizing enzyme that catalyzes rapid inactivation of corticosterone and cortisol to inert 11-keto derivatives. As 11beta-hydroxysteroid dehydrogenase type 2 is highly expressed in the developing brain, but not in the adult CNS, we hypothesized that it may represent a protective barrier to the deleterious actions of corticosteroids on proliferating cells. To test this hypothesis we have investigated the development and growth of the cerebellum in neonatal C57BL/6 mice and mice lacking 11beta-hydroxysteroid dehydrogenase type 2 (-/-). 11beta-Hydroxysteroid dehydrogenase type 2-/- mice had consistently lower body weight throughout the neonatal period, coupled with a smaller brain size although this was normalized when corrected for body weight. ⋯ Upon withdrawal of exogenous steroid, there was a rebound growth spurt so that at day 21 postnatally, the cerebellar size in 11beta-hydroxysteroid dehydrogenase type 2-/- mice was similar to untreated mice of the same genotype. Furthermore, 11beta-hydroxysteroid dehydrogenase type 2-/- mice had a delay in the attainment of neurodevelopmental landmarks such as negative geotaxis and eye opening. We therefore suggest that 11beta-hydroxysteroid dehydrogenase type 2 acts as to protect the developing nervous system from the deleterious consequences of glucocorticoid overexposure.
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Repeated cocaine administration in rats can lead to sensitization as evidenced by an increased locomotor response to a subsequent exposure (challenge) dose of cocaine even after a drug-free period. Expression of the immediate early gene product, c-Fos, differs among distinct subregions of the nucleus accumbens shell. This would suggest that these subregions may be differentially involved in sensitization. ⋯ Repeated cocaine administration resulted in robust sensitization that was associated with more deltaFosB in the vertex, arch, and cone compared with saline-treated controls. As previously reported, c-Fos immunoreactivity was increased in the intermediate zone in cocaine-sensitized rats. deltaFosB was significantly elevated in rats that did not receive a cocaine challenge, attesting to the long half-life of this transcription factor. These results provide further evidence suggesting distinct anatomical neuroadaptations within the nucleus accumbens shell that may play a functional role in psychomotor-stimulant sensitization.
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The amygdala plays a key role in emotional processing and anxiety-related physiological and behavioral responses. Previous studies have shown that injections of the anxiety-related neuropeptide corticotropin-releasing factor or the related neuropeptide urocortin 1 into the region of the basolateral amygdaloid nucleus induce anxiety-like behavior in several behavioral paradigms. Brainstem serotonergic systems in the dorsal raphe nucleus and median raphe nucleus may be part of a distributed neural system that, together with the basolateral amygdala, regulates acute and chronic anxiety states. ⋯ These behavioral effects were associated with increases in c-Fos expression within brainstem serotonergic neurons. In home cage rats and rats exposed to the social interaction test, urocortin 1 treatment increased the number of c-Fos-immunoreactive serotonergic neurons within subdivisions of both the dorsal raphe nucleus and median raphe nucleus. These results are consistent with the hypothesis that the basolateral amygdala and serotonergic neurons within the midbrain raphe complex are part of an integrated neural system modulating anxiety state.
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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.