Neuroscience
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Cannabinoid CB1 receptor (CB1R) signaling system is extensively distributed in the vertebrate retina. Activation of CB1Rs regulates a variety of functions of retinal neurons through modulating different ion channels. In the present work we studied effects of this receptor signaling on K(+) channels in retinal ganglion cells by patch-clamp techniques. ⋯ WIN-induced suppression of the K(+) currents was not observed when WIN was intracellularly applied. Furthermore, an endogenous ligand of the cannabinoid receptor anandamide, the specific CB1R agonist ACEA and the selective CB2R agonist CB65 also suppressed the K(+) currents, and the effects were not blocked by AM251/SR141716 or AM630 respectively. All these results suggest that the WIN-induced suppression of the outward K(+) currents in rat retinal ganglion cells, thereby regulating the cell excitability, were not through CB1R/CB2R signaling pathways.
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Prolonged and repeated periods of maternal separation produce behavioral phenotype of increased vulnerability to neuropsychiatric disorders and drug abuse. Most of the changes in behavior, corticosterone (CORT) and monoamine levels induced by long maternal separation (LMS) are observed after a challenge, but not in basal conditions. LMS increases ethanol-induced locomotor response and self-administration, possibly due to changes in CORT release and/or monoamine concentrations. ⋯ In LMS males, chronic ethanol increased hippocampal noradrenaline, dopamine, serotonin and metabolites when compared to respective AFR controls, as well as acute LMS. Moreover, chronic ethanol treatment resulted in higher CORT concentrations in LMS than in AFR males. Overall, these results indicate that LMS mice were more susceptible to the effects of chronic ethanol administration on CORT and brain monoamine concentrations, and that these effects were sex-dependent.
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It is reported that the amyloid-β protein (Aβ)-induced impairments in synaptic plasticity coincide with memory decline and dementia. Although Aβ-induced inhibition of hippocampal long-term potentiation has been intensively investigated, the underlying mechanism of Aβ-enhanced long-term depression (LTD) is not clear. Here, we report that acute exposure of rat hippocampal slices to soluble Aβ-enhanced LTD induced by weak low-frequency stimulation (wLFS; 1Hz for 3 min, 180 pulses) in granule cells of the dentate gyrus. ⋯ Application of either non-selective caspase inhibitor Z-VAD-FMK or caspase-3 selective inhibitor Z-DEVD-FMK prevented Aβ-enhanced LTD. However, neither the tumor necrosis factor-α converting enzyme inhibitor TAPI-2 nor the mammalian target of rapamycin inhibitor rapamycin prevented the enhancement of Aβ on LTD. Therefore, we conclude that soluble Aβ enhances LTD in the hippocampal dentate gyrus region, and the facilitatory effect of Aβ on LTD involves mGluR1/5, p38MAPK, STEP and caspase-3 activation.
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Mas oncogene-related gene (Mrg) G protein-coupled receptors are exclusively expressed in small-sized neurons in trigeminal and dorsal root ganglia (DRG) in mammals. The present study investigated the effect of MrgC receptor activation on morphine analgesic potency and addressed its possible mechanisms. Intrathecal (i.t.) administration of the specific MrgC receptor agonist bovine adrenal medulla 8-22 (BAM8-22, 3 nmol) increased morphine-induced analgesia and shifted the morphine dose-response curve to the left in rats. ⋯ The present study demonstrated that acute administration of morphine inhibited the repertoire of MOR/Gi-protein coupling in the spinal dorsal horn in vivo. The findings highlight a novel mechanism by which the activation of MrgC receptors can modulate the coupling of MORs with Gi-protein to enhance morphine-induced analgesia. Hence, adjunct treatment of MrgC agonist BAM8-22 may be of therapeutic value to relieve pain.
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Neuronal migration during brain development sets the position of neurons for the subsequent wiring of neural circuits. To understand the molecular mechanism regulating the migrating process, we considered the migration of mouse precerebellar neurons. Precerebellar neurons originate in the rhombic lip of the hindbrain and show stereotypic, long-distance tangential migration along the circumference of the hindbrain to form precerebellar nuclei at discrete locations. ⋯ We found that shRNA-mediated inhibition of Csde1 expression resulted in a failure of precerebellar neurons to complete their migration into their prospective target regions, with many neurons remaining in migratory paths. Furthermore, those that did reach their destination failed to invade the depth of the hindbrain via radial migration. These results have uncovered a crucial role of Csde1 in the proper control of both radial and tangential migration of precerebellar neurons.