Neuroscience
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Retinal bipolar cells relay visual information from photoreceptors to third-order retinal neurons. Bipolar cells, comprising multiple types, play an essential role in segregating visual information into multiple parallel pathways in the retina. The identification of molecular markers that can label specific retinal bipolar cells could facilitate the investigation of bipolar cell functions in the retina. ⋯ GFP expression in retinal cone bipolar cells was seen as early as postnatal day 5. In addition, despite severe retinal degeneration due to the presence of the rd1 mutation in this transgenic line, the density of GFP-labeled cone bipolar cells remained stable up to at least 6 months of age. This transgenic mouse line will be a useful tool for the study of type 4 cone bipolar cells in the retina under both normal and disease conditions.
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Cerebral ischemia/reperfusion injury is characterized by the development of inflammatory response, in which vascular macrophages and endogenous microglia are involved. Recent studies showed marked induction of hematopoietic prostaglandin D synthase (HPGDS) after ischemic/reperfusion injury and its localization in microglia, but the molecular mechanism(s) of HPGDS actions in cerebral ischemia is not clear. To clarify the role of HPGDS in cerebral ischemia, C57BL/6 mice and bone marrow chimera mice with cerebral ischemia/reperfusion injury were treated with (4-benzhydryloxy-(1) {3-(1H-tetrazol-5-yl)-propyl}piperidine (HQL-79), a specific inhibitor of HPGDS. ⋯ HQL-79 reduced NeuN expression in the transition area and Iba1 expression (P<0.0001) in the ischemic peri- and penumbra area, but increased COX-2 (P<0.05) and NF-kB expression (P<0.05) in ischemic penumbra and increased formation of nitrotyrosine (P<0.0001) and iNOS (P<0.0001) in the ischemic core area at 72 h and 7 days after reperfusion. In EGFP chimera mice, HQL-79 increased the migration of Iba1/EGFP-positive bone marrow-derived monocytes/macrophages, and simultaneously upregulated iNOS expression in the ischemic core area (P<0.0001), but increased intrinsic microglia/macrophages in ischemic peri-area and penumbra (P<0.0001) at 72 h and 7 days after reperfusion, suggesting involvement of monocytes/macrophages in HQL-79-induced expansion of ischemic injury. Our results demonstrated that the neuroprotective effects of HPGDS in our model are mediated by suppression of activation and infiltration of inflammatory cells.
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Recent studies have shown that in the pedunculopontine tegmental nucleus (PPT), increased neuronal activity and kainate receptor-mediated activation of intracellular protein kinase A (PKA) are important physiological and molecular steps for the generation of rapid eye movement (REM) sleep. In the present study performed on rats, phosphorylated cyclic AMP response element-binding protein (pCREB) immunostaining was used as a marker for increased intracellular PKA activation and as a reflection of increased neuronal activity. To identify whether activated cells were either cholinergic or noncholinergic, the PPT and laterodorsal tegmental nucleus (LDT) cells were immunostained for choline acetyltransferase (ChAT) in combination with pCREB or c-Fos. ⋯ These results provide evidence supporting the hypothesis that during REM sleep, the PPT cholinergic neurons are active, whereas the LC and DRN neurons are inactive. More importantly, the regression analysis indicated that pCREB activation in approximately 98% of PPT cholinergic neurons, was caused by REM sleep. Moreover the results indicate that during REM sleep, PPT intracellular PKA activation and a transcriptional cascade involving pCREB occur exclusively in the cholinergic neurons.
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The behavioral and motivational changes that result from use of abused substances depend upon activation of neuronal populations in the reward centers of the brain, located primarily in the corpus striatum in primates. To gain insight into the cellular mechanisms through which abused drugs reinforce behavior in the primate brain, changes in firing of neurons in the ventral (VStr, nucleus accumbens) and dorsal (DStr, caudate-putamen) striatum to "natural" (juice) vs. drug (i.v. cocaine) rewards were examined in four rhesus monkeys performing a visual Go-Nogo decision task. ⋯ Results show that neurons in the primate striatum encoded cocaine-rewarded trials similar to juice-rewarded trials, except for (1) increased firing on cocaine-rewarded trials, (2) prolonged activation during delivery of i.v. cocaine infusion, and (3) differential firing in ventral (VStr cells) vs. dorsal (DStr cells) striatum cocaine-rewarded trials. Reciprocal activations of antithetic subpopulations of cells during different temporal intervals within the same trial suggest a functional interaction between processes that encode drug and natural rewards in the primate brain.
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The transmembrane isoform of agrin (Tm-agrin) is the predominant form expressed in the brain but its putative roles in brain development are not well understood. Recent reports have implicated Tm-agrin in the formation and stabilization of filopodia on neurites of immature central and peripheral neurons in culture. In maturing central neurons, dendritic filopodia are believed to facilitate synapse formation. ⋯ We found that dendritic filopodia density was markedly reduced, as was synapse density along dendrites. Moreover, synapse formation was more sharply reduced on dendrites of infected neurons contacted by uninfected axons than on uninfected dendrites contacted by infected axons. The results are consistent with a physiological role for Tm-agrin in the maturation of hippocampal neurons involving positive regulation of dendritic filopodia and consequent promotion of synaptogenesis, but also suggest a role for axonal agrin in synaptogenesis.