Neuroscience
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Neuroimaging studies have established that there are losses in the volume of gray matter in certain cortical regions between adolescence and adulthood, with changes in the prefrontal cortex being particularly dramatic. Previous work from our laboratory has demonstrated that cell death can occur as late as the fourth postnatal week in the rat cerebral cortex. The present study examined the possibility that neuronal loss may occur between adolescence and adulthood in the rat prefrontal cortex. ⋯ In contrast to neuron number, the number of glial cells was stable in the ventral mPFC and increased between adolescence and adulthood in the dorsal mPFC. Sex-specific developmental changes in neuron number, glial number, and volume resulted in sex differences in adults that were not seen during adolescence. The loss of neurons at this time may make the peri-adolescent prefrontal cortex particularly susceptible to the influence of environmental factors.
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The binding of integrins to the extracellular matrix results in focal organization of the cytoskeleton and the genesis of intracellular signals that regulate vital neuronal functions. Recent evidence suggests that integrins modulate G-protein-coupled receptor (GPCR) signaling in hippocampal neurons. In this study we evaluated the hypothesis that integrins regulate the mu opioid receptor in rat trigeminal ganglion neurons. ⋯ Galphai vs. Galphas). Collectively, these data provide the first evidence that specific integrins regulate opioid receptor signaling in sensory neurons.
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Sensory information in the retina is transferred from rod and cone photoreceptors to higher visual centers via numerous parallel circuits that sample the photoreceptor mosaic independently. Each circuit consists of a unique combination of ganglion cell, bipolar and amacrine cell types. The morphology and physiological responses of many amacrine cells have been characterized. ⋯ The best-labeled GFP-expressing cell type in the INL was a wide-field amacrine cell that ramified in stratum 3. The GFP-expressing cells in the GCL resemble the type B1, or possibly A2 ganglion cells. The CD44-EGFP mice should provide a valuable resource for electrophysiological and connectivity studies of amacrine cells in the mouse retina.
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Chronic ethanol consumption produces a painful peripheral neuropathy. The aim of this study was then to investigate the mechanism underlying the neuropathic pain-like state induced by chronic ethanol treatment in rats. Mechanical hyperalgesia was clearly observed during ethanol consumption and even after ethanol withdrawal, and it lasted for, at least, 14 weeks. ⋯ Furthermore, total-MOR immunoreactivity was not changed in the spinal cord of ethanol-fed rats. Under these conditions, immunoblotting showed a robust increase in phosphorylated-cPKC immunoreactivity (p-cPKC-IR) in the spinal cord from chronic ethanol fed-rats, whereas phosphorylated-protein kinase A (PKA), dynamin II and G protein-coupled receptor kinase 2 (GRK2) were not affected in the spinal cord of ethanol-fed rats. These findings suggest that the dysfunction of MOR, but not DOR and KOR, linked to cPKC activation in the spinal cord may be, at least in part, involved in the reduced sensitivity to antinociception induced by morphine under the ethanol-dependent neuropathic pain-like state.
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The proinflammatory and potential neurotoxic cytokine tumor necrosis factor (TNF) is produced by activated CNS resident microglia and infiltrating blood-borne macrophages in infarct and peri-infarct areas following induction of focal cerebral ischemia. Here, we investigated the expression of the TNF receptors, TNF-p55R and TNF-p75R, from 1 to 10 days following permanent occlusion of the middle cerebral artery in mice. Using quantitative polymerase chain reaction (PCR), we observed that the relative level of TNF-p55R mRNA was significantly increased at 1-2 days and TNF-p75R mRNA was significantly increased at 1-10 days following arterial occlusion, reaching peak values at 5 days, when microglial-macrophage CD11b mRNA expression was also increased. ⋯ In situ hybridization revealed mRNA expression of both receptors in predominantly microglial- and macrophage-like cells in the peri-infarct and subsequently in the infarct, and being most marked from 1 to 5 days. Using green fluorescent protein-bone marrow chimeric mice, we confirmed that TNF-p75R was expressed in resident microglia and blood-borne macrophages located in the peri-infarct and infarct 1 and 5 days after arterial occlusion, which was supported by Western blotting. The data show that increased expression of the TNF-p75 receptor following induction of focal cerebral ischemia in mice can be attributed to expression in activated microglial cells and blood-borne macrophages.