Neuroscience
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This study aims to develop a transient ischemic attack (TIA) model in conscious animals and uses this model to investigate the effect of TIA on subsequent permanent ischemia. TIA was induced by injecting designed temperature-sensitive melted solid lipid microparticles with a melting point around body temperature into male Wistar rats via arterial cannulation. Neurologic deficit was monitored immediately after the injection without anesthesia. ⋯ The <24-h group had less severe neurologic deficits and smaller infarct volumes than that of 24-48-h and control (without prior lipid microparticle treatment) rats. Taken together, we successfully develop a TIA animal model which allows us to monitor the neurologic deficit in real-time. By adopting this model, we validate that TIA (<24h) preconditioning protects the brain from subsequent permanent ischemic stroke.
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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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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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Genipin, an important bioactive component from Gardenia jasminoides Eills, was demonstrated to possess antidepressant-like effects in a previous study. However, the molecular mechanism of antidepressant-like effects on genipin was not clear. The present study aimed to investigate the possible mechanism of antidepressant-like effects on genipin with a chronic unpredictable mild stress (CUMS)-induced depression model in rats. ⋯ The mRNA and protein expression of CREB, BDNF were increased in genipin-treated rats compared to the CUMS-exposed model group. Moreover, the levels of corticosterone in serum were decreased by genipin-treated compared to the CUMS-exposed model group. These results suggest that the possible mechanism of antidepressant-like effects on genipin, at least in one part, resulted from monoaminergic neurotransmitter system and the potential dysfunctional regulation of the post-receptor signaling pathway, which particularly affected the 5-HT(1A)R, 5-HT(2A)R and BDNF levels in the hippocampus.
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Cocaine abuse disrupts reward and homeostatic processes through diverse processes, including those involved in circadian clock regulation. Recently we showed that cocaine administration to mice disrupts nocturnal photic phase resetting of the suprachiasmatic (SCN) circadian clock, whereas administration during the day induces non-photic phase shifts. Importantly, the same effects are seen when cocaine is applied to the SCN in vitro, where it blocks photic-like (glutamate-induced) phase shifts at night and induces phase advances during the day. ⋯ Circadian patterns of SCN behavioral and neuronal activity did not differ between wild-type (WT) and SERT Met172 mice, nor did they differ in the ability of the 5-HT1A,2,7 receptor agonist, 8-OH-DPAT to reset SCN clock phase, consistent with the normal SERT expression and activity in the transgenic mice. However, (1) cocaine administration does not induce phase advances when administered in vivo or in vitro in SERT Met172 mice; (2) cocaine does not block photic or glutamate-induced phase shifts in SERT Met172 mice; and (3) cocaine does not induce long-term changes in free-running period in SERT Met172 mice. We conclude that SERT antagonism is required for the phase shifting of the SCN circadian clock induced by cocaine.