Neuroscience
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Sudden Infant Death Syndrome (SIDS) remains the leading cause of infant mortality in Western societies. A prior study identified an association between hearing suppression on the newborn hearing test and subsequent death from SIDS. This is the first finding of an abnormality in SIDS cases prior to death. A following study identified that inner ear dysfunction precipitates a marked suppression of the hypercapnic ventilatory response (HCVR). Failure of arousal has been proposed to be a key component in SIDS. The objective of the present study was to assess whether inner ear dysfunction not only weakens the hypercapnic response, but also plays a role in suppressing the arousal response to suffocating gas mixtures. ⋯ The findings support the theory that inner ear dysfunction could be relevant in the pathophysiology of SIDS. The inner ear appears to play a key role in arousal from suffocating gas mixtures that has not been previously identified.
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Perineuronal net (PNN) is a specialized aggregate of the extracellular matrix, which is considered to be involved in regulation of structural plasticity of neuronal circuits. Here we examined the spatial and temporal differences in Wisteria floribunda agglutinin-labeled PNN intensity in single cells in the mouse hippocampus, where the neuronal circuits engaged in cognition and emotion are embedded in the dorsal and ventral parts, respectively. In young mice, the intensity of PNN was very low, and there were no significant dorsoventral differences in all hippocampal regions. ⋯ Contrary to expectations, developmental and aging-related changes in PV intensity were not comparable to those seen in PNN intensity. The correlation coefficients between PNN and PV intensities in single cells showed gradual decline during development and aging in the CA1 and CA3 regions, while there were little correlations in the dentate gyrus regardless of age. In summary, PNNs are differentially expressed in the dorsal and ventral hippocampal circuits during development and aging, indicating their possible role for cognition and emotion control.
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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.