Neuroscience
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Trafficking or delivery of neurotransmitter receptors on postsynaptic membranes is critical for basal neurotransmission and synaptic plasticity. Importantly, dysfunction of such postsynaptic receptor trafficking can lead to severe brain diseases such as Alzheimer's Disease, autism spectrum disorder, and intellectual disability, yet underlying mechanisms remain elusive. One attractive hypothesis is that postsynaptic SNARE proteins play key roles in the delivery of receptors by mediating membrane fusion at postsynaptic neurons. ⋯ In this review, we propose to employ a pyramidal-neuron specific conditional knockout (cKO) model to study the roles of candidate SNARE proteins in postsynaptic receptor trafficking. We highlight our recent results which we obtained from such approaches to syntaxin-4 protein. These results provide clear evidence on the critical role of syntaxin-4 in trafficking of ionotropic glutamate receptors which are essential for basal neurotransmission, synaptic plasticity and spatial memory.
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Increasing studies have revealed that metabolic disorders, especially diabetes, are high risk factors for the development of Alzheimer's disease (AD) and other neurodegenerative diseases. It has been reported that patients with diabetes are prone to suffer from cognitive dysfunction (CD). Although abnormal glucose metabolism and deposition of amyloid β (Aβ) are proven to have a closely relationship with diabetes-induced CD, its exact mechanism is still undetermined. ⋯ Additionally, there were significant positive correlations between escape latency and p-YAP/YAP ratio in mPFC, anterior cingulate cortex (ACC) and hippocampus, as well as the level of LATS1 in liver, kidney and gut tissues. In conclusion, alterations in Hippo signaling may contribute to CD induced by diabetes. Therefore, therapeutic interventions improving Hippo signaling might be beneficial to the treatment of diabetes-induced CD and other neurodegenerative diseases.
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Repetitive mild traumatic brain injury (rmTBI; e.g., sports concussions) is common and results in significant cognitive impairment, white matter injury and increased risk of neurodegeneration. Targeted therapies for rmTBI are lacking, though evidence from other injury models indicates that targeting N-methyl-d-aspartate (NMDA) receptor (NMDAR)-mediated glutamatergic toxicity might mitigate rmTBI-induced injury. We have previously shown that the NMDAR antagonist memantine lessens axonal injury and restores long term potentiation after rmTBI. ⋯ Compared to vehicle-treated mice, memantine-treated mice were protected against oligodendrocyte loss and decreased MBP expression at subacute time points after injury. Memantine treatment also protected against axon damage assessed by NF-l expression. These data suggest that the therapeutic effects of post-concussive NMDAR antagonism may in part work through oligodendrocyte specific mechanisms, which may have implications for long term neurodegenerative sequelae after multiple concussions.
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The dorsolateral prefrontal cortex (DLPFC) is a crucial brain region for inhibitory control, an executive function essential for behavioral self-regulation. Recently, inhibitory control has been shown to be important for endurance performance. Improvement in inhibitory control was found following transcranial direct current stimulation (tDCS) applied over the left DLPFC (L-DLPFC). ⋯ Stroop task performance was improved after Real-tDCS as demonstrated by a lower number of errors for incongruent stimuli (p=0.012). TTE was significantly longer following Real-tDCS compared to Sham-tDCS (p=0.029, 17±8 vs 15±8min), with significantly lower HR (p=0.002) and RPE (p<0.001), while no significant difference was found for PAIN (p>0.224). ∆B[La-] was significantly higher at exhaustion in Real-tDCS (p=0.040). Our findings provide preliminary evidence that tDCS with the anodal electrode over the L-DLPFC can improve both inhibitory control and endurance cycling performance in healthy individuals.
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The current evidence suggests that aerobic fitness is associated with inhibitory control of executive functioning in children and older adults. However, the relative contributions of different neurophysiological mechanisms to this relation remain unclear and have not yet been examined in young adults. The present study aimed to compare inhibitory control between high and low-fit young adult men, and to investigate a possible mediation of fitness effects by conflict monitoring (N450 component of event-related potentials) and lateralized oxygenation difference (LOD) in the DLPFC. ⋯ In contrast, LOD was inversely correlated with Stroop interference, but did not explain the relation of aerobic fitness with behavioral performance. The present findings indicate that greater inhibitory control in high- compared to low-fit young men can be explained by more effective conflict monitoring. Moreover, young adults with left-lateralizedDLPFC oxygenation also show higher inhibitory control, but this oxygenation pattern is not influenced by aerobic fitness.