Neuroscience
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Recessive mutations in GRXCR2 cause deafness in both humans and mice. In Grxcr2 null hair cells, the sensory receptors for sound in the inner ear, stereocilia are disorganized. Reducing the expression of taperin, a protein that interacts with GRXCR2 at the base of stereocilia, corrects the morphological defects of stereocilia and restores hearing in Grxcr2 null mice. ⋯ Then Grxcr2 null mice were crossed with one of these taperin mutant mice. The following morphological analysis revealed that reducing taperin expression indeed corrected stereocilia morphological abnormalities in Grxcr2 null mice. Functional analysis further confirmed that reducing taperin expression partially restored hearing in Grxcr2 null mice.
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Increasing evidence has shown that early life events exert long-lasting effects on brain function and mental diseases. Exercise has been proven to have many positive effects on behaviors, such as reducing anxiety- and depression-like behaviors and alleviating cognitive impairment. However, the long-lasting and even short-term effects of regular swimming exercise on social dominance remain unclear. ⋯ There was no difference between the swimming and sedentary groups in anxiety- and depression-like behaviors. Metabolomics analysis showed that there were alterations in particular metabolites and signaling pathways after one month of swimming exercise, including sphingolipid metabolism, neuroactive ligand-receptor interaction and caffeine metabolism. In conclusion, our results provide the first evidence that postweaning swimming exercise has long-lasting and sex-dependent effects on social dominance, which may be caused by metabolic adaptation.
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Diffusion Tensor Imaging (DTI) and Manganese Enhanced MRI (MEMRI) are noninvasive tools to characterize neural fiber microstructure and axonal transport. A combination of both may provide novel insights into the progress of neurodegeneration. To investigate the relationship of DTI and MEMRI in white matter of tauopathy, twelve optic nerves of 11-month-old p301L tau mice were imaged and finished with postmortem immunohistochemistry. ⋯ Immunohistochemistry findings showed that ONAR, mD, and rD are significantly correlated with the myelin content (Myelin Basic Protein, p < 0.05) but not with the axonal density (SMI-31), tubulin density, or tau aggregates (AT8 staining). In summary, slower axonal transport appeared to have less myelinated axons and thinner remaining axons, associated with reduced rD and mD of in vivo DTI. A combination of in vivo MEMRI and DTI can provide critical information to delineate the progress of white matter deficits in neurodegenerative diseases.
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Although the exact etiology of Parkinson's disease (PD) is still unknown, there are a variety of treatments available to alleviate its symptoms according to the development stage of PD. Deep brain stimulation (DBS), the most common surgical treatment for advanced PD, accurately locates and implants stimulating electrodes at specific targets in the brain to deliver high-frequency electrical stimulation that alters the excitability of the corresponding nuclei. However, for different patients and stages of PD development, there exists a choice of the optimal DBS protocol. ⋯ Lastly, the evolution of the network state from normal to pathological is simulated. The critical point of network state transitions is determined. These results provide a quantitative and qualitative method for determining the optimal regimen for DBS for PD, which is helpful for clinical practice.
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Depression is a serious physical and mental disease, with major depressive disorder (MDD) being a hard-to-treat, life-threatening form of the condition. Currently, esketamine (ESK) is used in the clinical treatment of MDD, but the drug mechanisms continue to be unclear. In this study, we explored the therapeutic efficacy of ESK against lipopolysaccharide (LPS)-induced neuroinflammatory, autophagic, and depressive symptoms and the possible mechanisms behind them. ⋯ Furthermore, we were interested to know if ESK in combination with other autophagy inhibitors would have a better antidepressant effect, and we chose the autophagy inhibitor 3-MA for this attempt. Interestingly, the use of 3-MA did not attenuate or even enhance the therapeutic effect of ESK. The results suggest that, in the LPS-induced depression models, ESK conveyed an antidepressant effect via the inhibition of autophagy through the mTOR-BDNF pathway.