Neuroscience
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Lipopolysaccharide (LPS)-induced white matter injury in the neonatal rat brain is associated with inflammatory processes. Cyclooxygenase-2 (COX-2) can be induced by inflammatory stimuli, such as cytokines and pro-inflammatory molecules, suggesting that COX-2 may be considered as the target for anti-inflammation. The objective of the present study was to examine whether celecoxib, a selective COX-2 inhibitor, can reduce systemic LPS-induced brain inflammation and brain damage. ⋯ Celecoxib administration significantly attenuated systemic LPS-induced increments in the number of activated microglia and astrocytes, concentrations of IL-1β and TNFα, and protein levels of phosphorylated-p38 MAPK in the neonatal rat brain. The protection of celecoxib was also associated with a reduction of systemic LPS-induced COX-2+ cells which were double labeled with GFAP+ (astrocyte) cells. The overall results suggest that celecoxib was capable of attenuating the brain injury and neurobehavioral disturbance induced by systemic LPS exposure, and the protective effects are associated with its anti-inflammatory properties.
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The physiological effects of melanocortin-4 receptor (MC4-R) on metabolism have been hypothesized to be mediated individually or collectively by neuronal groups innervating the paraventricular nucleus of the hypothalamus (PVH). The present study was designed to identify MC4-R-expressing neurons that innervate the PVH using retrograde tract tracing techniques in the MC4-R-GFP reporter mice. Our initial mapping identified very limited projections from MC4-R-expressing neurons to the PVH. ⋯ Contrary to expectation, MC4-R-GFP neurons in the PMv do not respond to leptin as demonstrated by double labeling for GFP and leptin-induced phosphorylated STAT3. However, we found that Fos expression is induced in a large subset of MC4-R-GFP neurons in the PMv in response to opposite sex odors. Collectively, these results provide evidence for a previous unrecognized role of MC4-R expressed by neurons innervating the PVH that are also sensitive to reproductive cues.
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Vestibular afferent neurons (VANs) transmit information from the vestibular end organs to the central nuclei. This information is encoded within the firing pattern of these cells and is heavily influenced by the K⁺ conductances expressed by vestibular neurons. In the present study, we describe the presence of a previously unidentified Na⁺-activated K⁺ conductance (KNa) in these cells. ⋯ These results are also consistent with the immunolabeling of Slick and Slack protein in isolated vestibular neurons, in the vestibular ganglion and in the vestibular sensory epithelium. These results indicate that KNa channels are expressed in VANs and in their terminals. Furthermore, these data indicate that these channels may contribute to the firing pattern of vestibular neurons.
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The function of the sigma-1 receptor (S1R) has been implicated in modulating the activity of various ion channels. In the CNS S1R is enriched in cholinergic postsynaptic densities in spinal cord motoneurons (MNs). ⋯ Electrophysiological experiments demonstrate that MN of mice lacking S1R exhibit increased excitability. Taken together the data suggest the S1R acts as a brake on excitability, an effect that might enhance longevity in an ALS mouse model.
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Identification of markers of enteric neurons has contributed substantially to our understanding of the development, normal physiology, and pathology of the gut. Previously identified markers of the enteric nervous system can be used to label all or most neuronal structures or for examining individual cells by labeling just the nucleus or cell body. Most of these markers are excellent but have some limitations. ⋯ TMEM100 is also expressed in neuronal cell bodies and fibers in the mouse brain and dorsal root ganglia. We conclude that TMEM100 is a novel, membrane-associated marker for enteric nerves and is as effective as PGP9.5 for identifying neuronal structures in the gastrointestinal tract. The expression of TMEM100 in the enteric nervous system may reflect a role in the development and differentiation of cells through a transforming growth factor β, BMP or related signaling pathway.