Molecular brain
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One major interest in the study of transient receptor potential vanilloid type 1 (TRPV1) in sensory system is that it may serve as a drug target for treating chronic pain. While the roles of TRPV1 in peripheral nociception and sensitization have been well documented, less is known about its contribution to pain-related cortical plasticity. Here, we used 64 multi-electrode array recording to examine the potential role of TRPV1 in two major forms of synaptic plasticity, long-term potentiation (LTP) and long-term depression (LTD), in the anterior cingulate cortex (ACC). ⋯ Analysis of the results from different layers of the ACC obtained the same conclusions. Spatial distribution of LTP or LTD-showing channels among the ACC network was also unaltered by the TRPV1 antagonists. Since cortical LTP and LTD in the ACC play critical roles in chronic pain triggered by inflammation or nerve injury, our findings suggest that TRPV1 may not be a viable target for treating chronic pain, especially at the cortical level.
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Silver nanoparticles (AgNPs), owing to their effective antimicrobial properties, are being widely used in a broad range of applications. These include, but are not limited to, antibacterial materials, the textile industry, cosmetics, coatings of various household appliances and medical devices. Despite their extensive use, little is known about AgNP safety and toxicity vis-à-vis human and animal health. Recent studies have drawn attention towards potential neurotoxic effects of AgNPs, however, the primary cellular and molecular targets of AgNP action/s remain to be defined. ⋯ Taken together, our data show that AgNPs induce toxicity in neurons, which involves degradation of cytoskeleton components, perturbations of pre- and postsynaptic proteins, and mitochondrial dysfunction leading to cell death. Our study clearly demonstrates the potential detrimental effects of AgNPs on neuronal development and physiological functions and warns against its prolific usage.
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Several etiological reports have shown that chronic pain significantly interferes with sleep. Inadequate sleep due to chronic pain may contribute to the stressful negative consequences of living with pain. However, the neurophysiological mechanism by which chronic pain affects sleep-arousal patterns is as yet unknown. Although serotonin (5-HT) was proposed to be responsible for sleep regulation, whether the activity of 5-HTergic neurons in the dorsal raphe nucleus (DRN) is affected by chronic pain has been studied only infrequently. On the other hand, the recent development of optogenetic tools has provided a valuable opportunity to regulate the activity in genetically targeted neural populations with high spatial and temporal precision. In the present study, we investigated whether chronic pain could induce sleep dysregulation while changing the activity of DRN-5-HTergic neurons. Furthermore, we sought to physiologically activate the DRN with channelrhodopsin-2 (ChR2) to identify a causal role for the DRN-5-HT system in promoting and maintaining wakefulness using optogenetics. ⋯ These results suggest that neuropathic pain accelerates the activity of DRN-5-HTergic neurons. Although further loss-of-function experiments are required, we hypothesize that this activation in DRN neurons may, at least in part, correlate with sleep dysregulation under a neuropathic pain-like state.
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The transplantation of neural stem/progenitor cells (NS/PCs) at the sub-acute phase of spinal cord injury, but not at the chronic phase, can promote functional recovery. However, the reasons for this difference and whether it involves the survival and/or fate of grafted cells under these two conditions remain unclear. To address this question, NS/PC transplantation was performed after contusive spinal cord injury in adult mice at the sub-acute and chronic phases. ⋯ The extent of glial scar formation and the characteristics of inflammation is the most remarkable difference in the injured spinal cord microenvironment between the sub-acute and chronic phases. To achieve functional recovery by NS/PC transplantation in cases at the chronic phase, modification of the microenvironment of the injured spinal cord focusing on glial scar formation and inflammatory phenotype should be considered.
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Fear is one of the most potent emotional experiences and is an adaptive component of response to potentially threatening stimuli. Cumulative evidence suggests that the amygdala plays a central role in the acquisition, storage and expression of fear memory. We previously showed that the selective ablation of striatal neurons in the adult brain impairs the long-term, but not short-term, memory for auditory fear conditioning with a lower-intensity footshock. This finding raises an intriguing possibility that long-term auditory fear memory may be consolidated in the striatum. ⋯ These results suggest that NMDA receptors and de novo protein synthesis in the striatum are crucial for the consolidation of auditory fear memory formed with a low-intensity unconditioned stimulus.