Neuroscience
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Mitochondrial permeability transition pore (mPTP) opening is critical to mitochondrial apoptosis during ischemic injury. Sirtuin 3 (Sirt3) is a mitochondrial deacetylase known to play a major role in stress resistance and cell death. Our previous studies have shown that Sirt3 activates superoxide dismutase 2 and forkhead box O3a to reduce cellular reactive oxygen species. ⋯ Sirt3 overexpression suppressed the increase in VDAC1, ANT1 and cleaved caspase 3 that were induced by the serum and glucose deprivation (SGD) condition. Our studies suggest that ischemic injury induced mPTP opening and apoptosis by reducing Sirt3. It helps to identify new therapeutic targets for ischemic stroke.
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Although conditioned pain modulation (CPM) is considered to represent descending pain inhibitory mechanisms triggered by noxious stimuli applied to a remote area, there have been no previous studies comparing CPM between pain and tactile systems. In this study, we compared CPM between the two systems objectively using blink reflexes. Intra-epidermal electrical stimulation (IES) and transcutaneous electrical stimulation (TS) were applied to the right skin area over the supraorbital foramen to evoke a nociceptive or a non-nociceptive blink reflex, respectively, in 15 healthy males. ⋯ Both the NRS score and nociceptive R2 were significantly decreased in the third session for IES, with a significant correlation between the two variables; whereas, TS-induced non-nociceptive R2 did not change among the sessions. Although the conditioning stimulus decreased the NRS score for TS, the CPM effect was significantly smaller than that for IES (p = 0.002). The present findings suggest the presence of a pain-specific CPM effect to a heterotopic noxious stimulus.
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Inflammation plays a key role in the progression and maintenance of chronic pain, which impacts the lives of millions of Americans. Despite growing evidence that chronic pain can be improved by treating underlying inflammation, successful treatments are lacking and pharmaceutical interventions are limited due to drug side effects. Here we are testing whether a 'healthy human' diet (HHD), with or without anti-inflammatory components (HHAID), improves pain-like behaviors in a preclinical model of chronic widespread hypersensitivity induced by neonatal maternal separation (NMS). ⋯ In female mice, HHAID specifically increased measures of metabolic syndrome and inflammation compared to the HHD and control diet groups. Male mice were susceptible to worsening metabolic measures on both the HHAID and HHD. This work highlights important sexual dimorphic outcomes related to early life stress exposure and dietary interventions, as well as a potential disconnect between improvements in pain-like behaviors and metabolic measures.
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Face recognition is one of the most important cognitive functions for humans in social activities. The ability will be negatively affected when the face images deteriorate. However, the neural process of extracting facial information under challenging conditions is still poorly understood. ⋯ For each subject, the behavioral performance and magnitudes of the HGP for the face-specific sites significantly both fit a sigmoid function and showed similar changes. Additionally, the curve profile of the average HGP magnitude across the face-specific sites was almost equal to the average behavior curve; the former could precisely track the behavioral performance. In general, these results suggest that the HGP in the FG is closely related to the performance of face image recognition.
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Localization of sound sources in the environment requires neurons that extract interaural timing differences (ITD) in low-frequency hearing animals from fast and precisely timed converging inputs from both ears. In mammals, this is accomplished by neurons in the medial superior olive (MSO). MSO neurons receive converging excitatory input from both the ipsilateral and contralateral cochlear nuclei and glycinergic, inhibitory input by way of interneurons in the medial and lateral nuclei of the trapezoid body (MNTB and LNTB, respectively). ⋯ Herein, we utilized neuron reconstructions and immunohistochemistry to investigate the distribution of glutamatergic and glycinergic inputs onto human MSO neurons. Our results indicate that human MSO neurons have simple, symmetric dendrites and that glycinergic inputs outnumber glutamatergic inputs on MSO cell bodies and proximal dendrites. Together these results suggest that the human MSO utilizes similar circuitry to other mammals with excellent low-frequency hearing.