Neuroscience
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Melatonin, a neurohormone secreted mainly by the pineal gland, has a variety of physiological functions and neuroprotective effects. Previous studies have shown that melatonin could stimulate the proliferation of neural stem/progenitor cells (NS/PCs). Recent studies reported that the activities of mitogen-activated protein kinase (MAPK) of neural stem cells (NSCs) changed in response to the proliferative effect of melatonin. ⋯ The present results showed that melatonin could induce NS/PCs to proliferate by increasing phosphorylation of ERK1/2 and c-Raf through melatonin receptor. These results provide further evidence for a role of melatonin in promoting neurogenesis, adding to the remarkably pleiotropic nature of this neurohormone. This intrinsic modulator deserves further investigation to better understand its physiological and therapeutic implication.
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The laggard (lag) mutant mouse, characterized by hypomyelination and cerebellar ataxia, is a spontaneously occurring mutant mouse caused by mutation in the Kif14 gene. In this mutant mouse, the laminated structures such as the cerebral and cerebellar cortices and the dentate gyrus are cytoarchitecturally abnormal. Macroscopically, the olfactory bulb of the lag mutant mouse is smaller in size and more transparent than the normal counterpart. ⋯ In the mutant, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells in the subventricular zone of the lateral ventricle are increased in number, especially at perinatal age, suggesting that the decreased population of granule cells in the lag mutant mouse is caused by the increased apoptotic cell death. The olfactory input appears to be intact, as indicated by anterograde labeling of olfactory nerves with an injection of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) into the olfactory mucosa. In conclusion, the olfactory bulb of the lag mutant mouse is cytoarchitecturally affected, suggesting that the causal gene for lag mutation, i.e., Kif14, has multiple effects on the development of laminated structures in the central nervous system in addition to the myelin formation.
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Three structurally similar odorants trigger distinct signaling pathways in a mouse olfactory neuron.
In the mammalian olfactory system, one olfactory sensory neuron (OSN) expresses a single olfactory receptor gene. By calcium imaging of individual OSNs in intact mouse olfactory turbinates, we observed that a subset of OSNs (Ho-OSNs) located in the most ventral olfactory receptor zone can mediate distinct signaling pathways when activated by structurally similar ligands. Calcium imaging showed that Ho-OSNs were highly sensitive to 2-heptanone, heptaldehyde and cis-4-heptenal. 2-heptanone-evoked intracellular calcium elevation was mediated by cAMP signaling while heptaldehyde triggered the diacylglycerol pathway. ⋯ The feature that an olfactory receptor mediates multiple signaling pathways was specific for Ho-OSNs and not established in another population of OSNs characterized. Our study suggests that distinct signaling pathways triggered by ligand-induced conformational changes of an olfactory receptor constitute a complex information process mechanism in olfactory transduction. This study has important implications beyond olfaction in that it provides insights of plasticity and complexity of G-protein-coupled receptor activation and signal transduction.
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In the present study, we addressed the question of whether the up-regulation of laminin expression represents the astroglio-vascular responses to status epilepticus (SE) in the rat brain to better understand the role of vasogenic edema in epileptogenic insult. In the hippocampus, vasogenic edema was observed in the hippocampus 12h after SE when astroglial degeneration was undetected. Vasogenic edema in the hippocampus was more severe in the CA1 region where astroglial loss was absent than in the dentate gyrus showing astroglial degeneration. ⋯ Four weeks after SE, laminin expression was reduced in vessels showing strong SMI-71 expression within vasogenic edema lesion. Inhibition of SE-induced vasogenic edema formation by BQ788 effectively prevented laminin over-expression. Therefore, our findings indicate that laminin over-expression may be one of consequences from vasogenic edema rather than astroglial loss, and that laminin over-expression may promote migration of astrocytes to damaged or newly generated vessels to repair brain-blood barrier (BBB) disruption accompanied by the reconstruction of endothelial barrier.
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Intrauterine infection or inflammation in preterm neonates is a known risk for adverse neurological outcomes, including cognitive, motor and behavioral disabilities. Our previous data suggest that there is acute fetal brain inflammation in a mouse model of intrauterine exposure to lipopolysaccharides (LPS). We hypothesized that the in utero inflammation induced by LPS produces long-term electroencephalogram (EEG) biomarkers of neurodegeneration in the exposed mice that could be determined by using continuous quantitative video/EEG/electromyogram (EMG) analyses. ⋯ Sleep microstructure also showed significant alteration in the LPS mice specifically during the dark cycle, caused by significantly longer average non-rapid eye movement (NREM) cycle durations. No significance was found between treatment groups for the delta power data; however, significant activity-dependent changes in theta-beta power ratios seen in controls were absent in the LPS-exposed mice. In conclusion, exposure to in utero inflammation in CD1 mice resulted in significantly altered sleep architecture as adults that were circadian cycle and activity state dependent.