Neuroscience
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Previous studies from our laboratory have shown that 17beta-estradiol (E2) promotes neurite outgrowth in hippocampal and cortical neurons. The neurotrophic effect of E2 seen in vitro has also been observed in vivo by other investigators who found that E2 enhances the density of dendritic spines involved in neuronal synaptic connection. To investigate the rapid upstream mechanisms initiating the E2 neurotrophic effect, we tested the hypothesis that E2 would directly activate Ca2+ influx in primary hippocampal neurons, which would result in activation of the transcription factor, cyclic AMP response element-binding protein (CREB), and regulate E2 enhancement of neurite outgrowth. ⋯ E2-induced increase in dendritic spine marker protein spinophilin was abolished following treatment with a small interfering RNA against CREB, indicating that E2-induced neurotrophic effect requires the upstream CREB activation. Results of these analyses indicate that E2-induced neurotrophic responses are mediated by a Ca2+ signaling cascade that is dependent upon extracellular Ca2+ and CREB activation. These data provide insights into the initiating mechanisms required to activate the estrogen neurotrophic response and provide a mechanistic framework for determining the neurotrophic efficacy of existing and emerging estrogen therapies for the brain.
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Rats maintained under restricted feeding schedules (RFS) develop food-anticipatory activity and entrainment of physiological parameters. Food entrainment is independent of the suprachiasmatic nucleus and depends on food-entrainable oscillators (FEO). Restricted feeding schedules lead animals toward a catabolic state and to increase their food driven motivation, suggesting that in this process metabolic- and reward-related mechanisms are implicated. ⋯ Glucose and free fatty acids were not entrained in PME rats. c-Fos expression in limbic system nuclei was in phase with PME time, but not in the hypothalamus. Results suggest 1) that food deprivation, i.e. a catabolic state is not necessary for the expression of anticipatory activity; 2) that an increase in the motivational state due to taste and/or nutritional contents of palatable meal is sufficient to entrain behavior; and 3) that structures in the limbic system are involved in this entrainment process. The present study indicates that metabolic and motivational mechanisms are involved in food entrainment, and suggests that the FEO may be a multi-oscillatory system distributed over different regulatory systems in the brain.
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Converging evidence from different functional imaging studies indicates that the intensity of activation of different nociceptive areas (including the operculoinsular cortex, the primary somatosensory cortex, and the anterior cingulate gyrus) correlates with perceived pain intensity in the human brain. Brief radiant laser pulses excite selectively Adelta and C nociceptors in the superficial skin layers, provide a purely nociceptive input, and evoke brain potentials (laser-evoked potentials, LEPs) that are commonly used to assess nociceptive pathways in physiological and clinical studies. Adelta-related LEPs are constituted of different components. ⋯ We found that the amplitude of the N1 component correlated significantly with the subjective pain ratings, both within and between subjects. Furthermore, we showed that the N2 and P2 late LEP components are differentially sensitive to the perceived sensation, and demonstrated that the N2 component mainly explains the previously described correlation between perceived pain and the amplitude of the N2-P2 vertex complex of LEPs. Our findings confirm the notion that pain intensity processing is distributed over several brain areas, and suggest that the intensity coding of a noxious stimulus occurs already at the earliest stage of perception processing, in the operculoinsular region and, possibly, the primary somatosensory area.
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Comparative Study
Gender and environmental effects on regional brain-derived neurotrophic factor expression after experimental traumatic brain injury.
Alterations in brain-derived neurotrophic factor expression have been reported in multiple brain regions acutely after traumatic brain injury, however neither injury nor post-injury environmental enrichment has been shown to affect hippocampal brain-derived neurotrophic factor gene expression in male rats chronically post-injury. Studies have demonstrated hormone-related neuroprotection for female rats after traumatic brain injury, and estrogen and exercise both influence brain-derived neurotrophic factor levels. Despite recent studies suggesting that exposure post-traumatic brain injury to environmental enrichment improves cognitive recovery in male rats, we have shown that environmental enrichment mediated improvements with spatial learning are gender specific and only positively affect males. ⋯ In the hippocampus contralateral to injury, there were also significant injury-related increases in brain-derived neurotrophic factor expression for females (P
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Cell death was assessed by quantitative analysis of propidium iodide uptake in rat hippocampal slice cultures transiently exposed to oxygen and glucose deprivation, an in vitro model of brain ischemia. The hippocampal subfields CA1 and CA3, and fascia dentata were analyzed at different stages from 0 to 48 h after the insult. Cell death appeared at 3 h and increased steeply toward 12 h. ⋯ Both P2X receptors and N-methyl-D-aspartate receptors mediate influx of calcium. Our results suggest that inhibition of P2X receptors has a neuroprotective potential similar to that of inhibition of N-methyl-D-aspartate receptors. In contrast, our comparative analysis shows that only partial protection can be achieved by inhibiting the extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase cascade, one of the downstream pathways activated by intracellular calcium overload.