Neuroscience
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Icariin (ICA), a flavonoid extracted from the traditional Chinese herb Herba Epimedii that can freely cross the blood-brain barrier, inhibits neuroinflammation and attenuates oxidative stress damage. Our previous studies demonstrated that icariin exerts an antidepressant-like activity in a social defeat mouse model. However, it is unknown whether icariin is beneficial for the treatment of depression via its modulation of oxidative stress and neuroinflammation. ⋯ Interestingly, icariin negatively regulated the activation of the nod-like receptor protein 3 (NLRP3) inflammasome/caspase-1/IL-1β axis in the hippocampus of CMS rats. These results confirm that icariin exerts antidepressant-like effects, which may be mediated, at least in part, by enhanced antioxidant status and anti-inflammatory effects on the brain tissue via the inhibition of NF-κB signaling activation and the NLRP3-inflammasome/caspase-1/IL-1β axis. Our findings provide new information to understand the antidepressant action of icariin, which is targeted to the NLRP3-inflammasom in brain.
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Multiple sclerosis (MS) is thought to result from a combination of genetics and environmental factors. Several lines of evidence indicate that significant prevalence of anxiety and depression-related disorders in MS patients can influence the progression of the disease. Although we and others have already reported the consequences of prenatal maternal immune activation on anxiety and depression, less is known about the interplay between maternal inflammation, MS and gender. ⋯ Interestingly, the severity of the disease was associated with increased anxiety/depressive-like behaviors and elevated corticosterone or TNF-α levels in both sexes. Overall, these data suggest that maternal immune activation with Poly I:C during mid-pregnancy increases anxiety- and depressive-like behaviors, and the clinical symptoms of EAE in a sex-dependent manner in non-EAE or EAE-induced offspring. Finally, the progression of EAE in offspring seems to be linked to maternal immune activation-induced dysregulation in neuro-immune-endocrine system.
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Parkinson's disease (PD) is characterized by selective loss of dopaminergic neurons in the substantia nigra (SN). Epidemiological evidence has suggested a link between type 2 diabetes and PD, although the mechanisms remain largely unknown. We applied LC-MS/MS-based pattern analysis to investigate altered proteomes in the SN of db/db mice (db-SN) and high-fat diet mice (HFD-SN), revealing that the level of mitochondrial proteins has changed in the SN of diabetic mice compared to that of control mice. ⋯ Interestingly, these alterations were reversed by the administration of metformin, one of most frequently prescribed anti-hyperglycemic agents. The slight loss of dopaminergic neurons was found in chronic HFD-SN that was restored by metformin. Taken together, our data suggest that the dysregulation of Parkin-PARIS-PGC-1α pathway by metabolic malregulation may contribute to the pathogenesis of PD and metformin might exert a neuroprotective effect on PD via the restoration of parkin.
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Local circuits within the striatum of the basal ganglia include a small number of γ-aminobutyric acid (GABA)-ergic fast-spiking interneurons (FSI). The number of these cells is reduced in disorders of behavioral control, but it is unknown whether this is accompanied by altered electrophysiological properties. The genetically hypertensive (GH) rat strain exhibits impulsiveness and hyperactivity. ⋯ Putative FSI (pFSI) were encountered less often in GH rats compared to the Wistar control strain. pFSI in GH rats also exhibited a higher mean firing rate, higher intraburst firing rate, lower interburst interval, and shorter bursts compared to controls. AMPH increased the mean overall firing rate of Wistar rat pFSI but did not significantly alter the firing properties of this subtype in GH rats. These differences in the resting-state electrophysiological activity of pFSI in GH rats point to them as a cell type of particular interest in understanding striatal functioning across different strains.
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The medial parabrachial nucleus (MPB) and external part of the medial parabrachial nucleus (MPBE) relay gustatory, oral mechanosensory and other visceral information in the rat brain and reportedly project not only to the parvicellular part of the posteromedial ventral thalamic nucleus (VPMpc) but also to the ventrocaudal part of the intralaminar thalamic nuclei. Generally, the intralaminar thalamic nuclei project topographically to the caudate putamen (CPu); however, it is unclear where the ventrocaudal part of the intralaminar thalamic nuclei projects within the CPu. Thus, we visualized neural pathways from the MPB and MPBE to the CPu via the ventrocaudal part of the intralaminar thalamic nuclei using an anterograde tracer, biotinylated dextran amine, and a retrograde tracer, cholera toxin B subunit. ⋯ Further, we found that the VPMpc rather projected to the interstitial nucleus of the posterior limb of the anterior commissure than the CPu. The ventral part of the CPu is reported to be involved in jaw movement as well as food and water intake functions. Therefore, these parabrachio-thalamo-striatal pathways that we demonstrated here suggest that gustatory and oral mechanosensory information affects feeding behavior within the ventral part of the CPu.