Neuroscience
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Increasing evidence points to an essential role played by neuron-derived neurosteroids, such as estrogen, on synaptic connectivity in the hippocampus. Inhibition of local estradiol synthesis results in synapse loss specifically in females, but not in males. ⋯ Cognitive deficits after inhibition of aromatase, the final enzyme of estrogen synthesis, have been seen in women, but not in men. Altogether, the data demonstrate distinct differences between genders in neurosteroid-induced synaptic stability.
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Inosine (hypoxanthine 9-beta-D-ribofuranoside), a purine nucleoside with multiple intracellular roles, also serves as an extracellular modulatory signal. On neurons, it can produce anti-inflammatory and trophic effects that confer protection against toxic influences in vivo and in vitro. The protective effects of inosine treatment might also be mediated by its metabolite urate. ⋯ Urate concentration was not significantly increased by inosine treatment however there was a significant increase in levels of other purine metabolites, such as adenosine, hypoxanthine and xanthine. In particular, in MES 23.5-astrocytes co-cultures, inosine medium content was reduced by 99% and hypoxanthine increased by 127-fold. Taken together these data raise the possibility that inosine might have a protective effect in PD that is independent of any effects mediated through its metabolite urate.
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Sleep/wake disorders are frequently associated with anxiety and depression and to elevated levels of cortisol. Even though these alterations are increasingly sought in animal models, no study has investigated the specific effects of chronic corticosterone (CORT) administration on sleep. We characterized sleep/wake disorders in a neuroendocrine mouse model of anxiety/depression, based on chronic CORT administration in the drinking water (35 μg/ml for 4 weeks, "CORT model"). ⋯ With regard to REM sleep, the number and the duration of episodes decreased, specifically during the first part of the light period. REM and NREM sleep changes correlated respectively with the anxiety and the anxiety/depressive-like phenotypes, supporting the notion that studying sleep could be of predictive value for altered emotional behavior. The chronic CORT model in mice that displays hallmark characteristics of anxiety and depression provides an insight into understanding the changes in overall sleep architecture that occur under pathological conditions.
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Preterm infants are prematurely subjected to relatively high oxygen concentrations, even when supplemental oxygen is not administered. There is increasing evidence to show that an excess of oxygen is toxic to the developing brain. Dextromethorphan (DM), a frequently used antitussive agent with pleiotropic mechanisms of action, has been shown to be neuroprotective in various models of central nervous system pathology. ⋯ In vivo caspase-3 activation induced by hyperoxic exposure was significantly lower after administration of DM in gray and white matter areas. In control animals kept under normoxic conditions DM did not significantly influence caspase-3-dependent apoptosis. The present results indicate that DM is a promising and safe treatment strategy for neonatal hyperoxia-induced brain injury that merits further investigation.
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We used the cheek model of itch and pain in rats to determine the dose-response relationships for intradermal injection of serotonin and α methylserotonin on scratching behavior. We also determined the dose-related effects of intracisternally injected morphine on scratching, effects that were greatly reduced by administration of the opiate antagonist naloxone. We then examined the interactions of intradermal injection of serotonin and intracisternal injection of morphine on scratching and found that the two procedures act synergistically to increase itch. These results suggest that morphine applied to the CNS is capable of producing itch and greatly increasing itch originating in the skin (hyperknesis).