Neuroscience
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The ventrolateral preoptic area of the hypothalamus (VLPO) contains a population of sleep-active neurons and is hypothesized to be an important part of the somnogenic process. Adenosine (AD) is an endogenous sleep-promoting factor and may play an important role in promoting natural sleep. We hypothesize that AD may promote sleep, in part, by activating the VLPO sleep-active neurons. ⋯ In contrast, AD decreased EPSC frequency in seven cells (36-73%; mean=59%), increased frequency in five cells (30-236%; mean 83%) and had no effect in six cells. AD application increased the firing rate in two of four cells tested. These data are consistent with the hypothesis that one mechanism which AD may promote sleep is by blocking inhibitory inputs on VLPO sleep-active neurons.
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Hepatocyte growth factor as an enhancer of nmda currents and synaptic plasticity in the hippocampus.
Hepatocyte growth factor (HGF) promotes the survival and migration of immature neurons, but its role in the mature brain has remained elusive. In the hippocampus of juvenile rats, we found that the HGF receptor c-Met was expressed in neurons. Furthermore, it was highly Tyr-phosphorylated, more so than in the liver under normal conditions, suggesting that the receptor is activated and that HGF may act continuously in the intact brain. ⋯ We further found that HGF augmented N-methyl-D-aspartate receptor-mediated currents in both slices and dissociated neurons. This augmentation is likely to underlie the enhancement of LTP. Considering that the expression of both HGF and c-Met are known to be induced by ischemic stimuli, this modulation would provide a novel understanding of a neuronal regulatory systems shared with pathogenic ischemic states.
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Polyimide regenerative electrodes (RE) constitute a promising neural interface to selectively stimulate regenerating fibers in injured nerves. The characteristics of the regeneration through an implanted RE, however, are only beginning to be established. It was recently shown that the number of myelinated fibers distal to the implant reached control values 7 months postimplant; however, the functional recovery remained substantially below normal [J Biomed Mater Res 60 (2002) 517]. ⋯ Moreover, smaller ganglion cells regenerated better than large neurons by a significant 13.8%. These results indicate that the RE is not an obstacle for the re-growth of sensory fibers, but partially hinders fiber regeneration from motoneurons. They also suggest that fine fibers may be at an advantage over large ones to regenerate through the RE.
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The emerging profile for the effects of prenatal cocaine exposure presents two prominent features in the exposed offspring: cognitive/attention deficits and an age-associated trend toward motor/tone abnormalities up to 2 years of age. One candidate mechanism underlying these clinical features is long-lasting alterations to dopamine (DA) neuron function. However, the impact of prenatal cocaine exposure on DA release in dopaminergic terminal fields in vivo in mature offspring is poorly understood. ⋯ We also measured total dopamine transporter (DAT) and tyrosine hydroxylase protein levels in these offspring by blot immunolabeling and found a small, but significant, decrease in DAT protein in striatum from offspring exposed at GD 8-21 and GD 15-21. Collectively, these data demonstrate that prenatal cocaine exposure during dopamine neuron neurogenesis has long-lasting effects on DA neuron function lasting into early adulthood which may be related in part to steady state DAT protein levels. These molecular events may be associated with established cognitive deficits and perhaps the trends seen in altered motor behavior.
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Desensitization of post-synaptic serotonin1A (5-HT1A) receptors may underlie the clinical improvement of neuropsychiatric disorders. In the hypothalamic paraventricular nucleus, Galphaz proteins mediate the 5-HT1A receptor-stimulated increases in hormone release. Regulator of G protein signaling-Z1 (RGSZ1) is a GTPase-activating protein selective for Galphaz proteins. ⋯ Interestingly, previous experiments indicate that only estradiol produces a decreased Emax of 5-HT1A receptor-stimulation of hormone release, whereas fluoxetine, cocaine and DOI produce a shift to the right (increased ED50). Thus, the desensitization of 5-HT1A receptors by estradiol might be attributable to increased levels of RGSZ1 protein. These findings may provide insight into the adaptation of 5-HT1A receptor signaling during pharmacotherapies of mood disorders in women and the well-established gender differences in the vulnerability to depression.