Neuroscience
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We compared the efficacy of a modified truncated 24-aa peptide (TFP5), derived from the cyclin-dependent kinase 5 (CDK5)-activating cofactor p35, with mild hypothermia (MH), and determined whether the efficacy of TFP5 is affected by MH. ⋯ TFP5 is comparable to MH in improving neurological outcomes in early-stage adult ischemic stroke. When TFP5 is given along with MH, less neurological deficit tends to be achieved.
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Decreased proteolytic clearance of soluble amyloid β (Aβ) in microglia affects Aβ accumulation on Alzheimer's disease progression. However, the potential molecular mechanism by which microglial Aβ uptake is regulated remains unclear. In this study, we identified a microRNA, miR-124, that was down-regulated in aging with a function in regulating apolipoprotein E (ApoE)-dependent Aβ uptake by targeting regulatory factor X1 (RFX1) transcripts on BV2 microglia cell. ⋯ We also identified a miR-124 binding site in the 3'-UTR of RFX1 mRNA and a RFX1 binding site in the first intron of ApoE gene. Furthermore, interfering this signaling pathway by knocking down RFX1 significantly improved Aβ uptake in BV2 cells. These data demonstrate the mechanism through which decreased miR-124 expression under oxidative stress slowed Aβ uptake and suggest that RFX1 might be a target for improving Aβ clearance during aging.
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The aging process and menopausal transition are important factors in sexual dysfunction of menopausal women. No neuroimaging study has assessed the age- and menopause-related changes on brain activation areas associated with sexual arousal in menopausal women. The purpose of this study was to evaluate the time course of regional brain activity associated with sexual arousal evoked by visual stimulation in premenopausal and menopausal women, and further to assess the effect of menopause on the brain areas associated with sexual arousal in menopausal women using functional magnetic resonance imaging (fMRI). ⋯ Blood-oxygen-level-dependent signal changes in the amygdala while viewing erotic video were positively correlated with estrogen levels in the two groups. Our findings suggest that reduced brain activity of the thalamus, amygdala, and ACC in menopausal women may be associated with menopause-related decrease in sexual arousal. These findings might help elucidate the neural mechanisms associated with sexual dysfunction in menopausal women.
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Transcranial direct current stimulation (tDCS) is a common method to modulate cortical activity. Anodal tDCS is usually associated with an enhancement of the stimulated brain area, whereas cathodal tDCS is often described as inhibitory brain stimulation method. Our aim was to investigate whether this canonical assumption derived from the motor system could be transferred to the semantic system. ⋯ Recently, a meta-analysis revealed that the canonical anodal excitation and cathodal inhibition assumption is observed rarely in cognitive studies. In particular, an inhibitory effect of cathodal tDCS on cognition is rare. Our findings thus support the speculation, that especially language functions could be somewhat 'immune' to cathodal inhibition.
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Absence seizures arise from disturbances within the corticothalamocortical network, however the precise cellular and molecular mechanisms underlying seizure generation arising from different genetic backgrounds are not fully understood. While recent experimental evidence suggests that changes in inhibitory microcircuits in the cortex may contribute to generation of the hallmark spike-wave discharges, it is still unclear if altered cortical inhibition is a result of interneuron dysfunction due to compromised glutamatergic excitation and/or changes in cortical interneuron number. The stargazer mouse model of absence epilepsy presents with a genetic deficit in stargazin, which is predominantly expressed in cortical parvalbumin-positive (PV(+)) interneurons, and involved in the trafficking of glutamatergic AMPA receptors. ⋯ Further analysis using confocal fluorescence microscopy revealed that although there are no changes in cortical PV(+) interneuron number, there is a predominant loss of GluA1 and 4 containing AMPA receptors in PV(+) neurons in stargazers compared to non-epileptic controls. Taken together, these data suggest that the loss of AMPA receptors in PV(+) neurons could impair their feed-forward inhibitory output, ultimately altering cortical network oscillations, and contribute to seizure generation in stargazers. As such the feed-forward inhibitory interneurons could be potential targets for future therapeutic intervention for some absence epilepsy patients.