Neuroscience
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Apart from reproduction, estrogen influences a multitude of processes. Increase in estrogen levels in women is known to promote reward probably mediated via the melanocortin and dopamine systems. Reduced estrogen in post-menopausal women attenuates reward, evoking the need for stimulation with greater rewarding salience. ⋯ Prior treatment with sub-effective doses of α-MSH or NDP-MSH potentiated the reward effect of nicotine, but was attenuated by HS014. Alpha-MSH-immunoreactivity was decreased in the Acb shell, arcuate and paraventricular nucleus of hypothalamus, and ventral bed nucleus of stria terminalis in the OVX rats, while nicotine treatment restored the same. We suggest a role for the endogenous MC system, perhaps acting via MC4-R, in the nicotine-induced reward in OVX rats.
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The NOD-like receptor family Pyrin domain-containing 3 (NLRP3) inflammasome has a crucial role in the inflammatory process that occurs during intracerebral hemorrhage (ICH)-induced injury. Histone deacetylase 10 (HDAC10) is a newly identified class II histone deacetylase involved in immune responses. However, how HDAC10 affects the inflammatory response after ICH remains unknown. ⋯ Furthermore, HDAC10 silencing also promoted the interaction of PTPN22 and NLRP3. Our study demonstrated that HDAC10 silencing aggravated NLRP3-mediated inflammatory responses after ICH in rats via the PTPN22 pathway. These results suggest that regulating the NLRP3 inflammasome may be a novel method to ameliorate ICH injury.
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Focal cerebral infarction leads to autophagic activation, which contributes to secondary neuronal damage in the ipsilateral thalamus. Although Nogo-A deactivation enhances neuronal plasticity, its role in autophagic activation in the thalamus after ischemic stroke remains unclear. This study aimed to investigate the potential roles of Nogo-A/Nogo-66 receptor 1 (NgR1) in autophagic activation in the ipsilateral thalamus after cerebral infarction. ⋯ In contrast, NEP1-40 treatment significantly reduced the expression of Rho-A and ROCK1 which was accompanied by marked reductions of LC3-II conversion as well as the levels of Beclin1 and SQSTM1/p62. Furthermore, NEP1-40 treatment significantly reduced neuronal loss and gliosis in the ipsilateral thalamus, and accelerated somatosensory recovery at the observed time-points after MCAO. These results suggest that blockade of Nogo-A-NgR1 signaling inhibits autophagic activation, attenuates secondary neuronal damage in the ipsilateral thalamus, and promotes functional recovery after focal cerebral cortical infarction.
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Cochlear ribbon synapses formed between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) are immature at birth and they require dramatic morphological and functional developments to achieve auditory maturation in postnatal mice. However, the mechanism underlying this remodeling process of cochlear ribbon synapse remains elusive. Here, we report that autophagy is necessary for the development and maturation of cochlear ribbon synapses in mice. ⋯ Moreover, abnormal morphology of cochlear ribbon synapses and reduced IHC exocytosis function were detected from P15 to P30, which were likely associated to hearing impairment. Thus, our study demonstrated that autophagy was required for remodeling of cochlear ribbon synapses and provided a new insight into autophagy-related hearing disorder during auditory development. Furthermore, we implicated a novel therapeutic target for sensorineural hearing loss.
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Analysis of expression of the immediate early gene c-Fos in neuronal populations is a commonly used method to assess changes in neuronal activity due to various factors of interest. However, different levels of c-Fos have been observed between control animals across studies. The present investigation assessed whether such differences could reflect different behavioral or physiological states in housing conditions that are typically considered naïve controls. ⋯ Taken together, our experiment identified differential regulation of c-Fos expression by basal housing conditions and circadian phase. It also indicates that despite the well-known habituation of c-Fos expression to repeated stimulation, this expression is sensitive to basal housing conditions. This sensitivity needs to be taken into account when analyzing c-Fos data in various studies.