Neuroscience
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Primary somatosensory cortex (S1) contains a nociceptive map that localizes potential tissue damage on the body and encodes stimulus intensity. An objective and specific biomarker of pain however is currently lacking and is urgently required for use in non-verbal clinical populations as well as in the validation of pre-clinical pain models. Here we describe studies to see if the responses of the S1 in juvenile rats are different to those in the adult. ⋯ Noxious heat evoked a significant increase in theta band (4-8 Hz) activity in adults only (P<0.0001 compared to baseline; P<0.0001 compared to juveniles). There were no significant differences in EEG responses to innocuous thermal stimuli. These data show that there are significant alterations in the processing of nociceptive inputs within the maturing cortex and that cortical theta activity is involved only in the adult cortical response to noxious stimulation.
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Identifying novel biomarkers of resilience or vulnerability to stress could provide valuable information for the prevention and treatment of stress-related psychiatric disorders. To investigate the utility of blood microRNAs as biomarkers of resilience or vulnerability to stress, microRNAs were assessed before and after 7days of chronic social defeat in rats. Additionally, microRNA profiles of two important stress-regulatory brain regions, the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA), were assessed. ⋯ In the BLA, 77 microRNAs were significantly altered by stress but none were significantly different between resilient and vulnerable animals. These results provide proof-of-principle that assessment of circulating microRNAs is useful in identifying individuals who are vulnerable to the effects of future stress or individuals who have become resilient to the effects of stress. Furthermore, these data suggest that microRNAs in the mPFC but not in the BLA are regulators of resilience/vulnerability to stress.
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The activation of renin angiotensin system is involved in multiple pathological processes. The neuroprotective effect of propofol has been reported. We hypothesized that propofol may attenuate Angiotensin II (Ang II)-induced apoptosis in mouse hippocampal HT22 cells and aimed to identify the underlying mechanisms. ⋯ Ang II via AT1R induced oxidative stress and apoptosis in hippocampal HT22 cells, and the neuroprotective anti-apoptotic effect of propofol was mediated through inhibiting oxidative stress.
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Numerous studies have indicated dental pulp stem cells (DPSCs) potency to differentiate into several types of cell lineages. Oligodendrocyte lineage transcription factor 2 (OLIG2) plays an important role in the oligodendrogenic pathway. In this study, a tetracycline (Tet)-inducible system expressing OLIG2 gene was transfected into human DPSCs to direct their differentiation toward oligodendrocyte progenitor cells (OPCs). ⋯ Improvement of behavioral symptoms was efficiently observed from the second week to the sixth week post-transplantation. Our findings showed that exogenous expression of the OLIG2 gene by a Tet-regulated system could be used as an efficient way to induce the differentiation of DPSCs into functional oligodendrocytes. Meanwhile, the DPSC-derived OPCs have relevant therapeutic potential in the animal model of sciatic nerve injury and therefore might represent a valuable tool for stem cell-based therapy in inflammatory and degenerative diseases of the peripheral and central nervous systems (CNSs).
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Osteoarthritis (OA) remains one of the greatest healthcare burdens in western society, with chronic debilitating pain-dominating clinical presentation yet therapeutic strategies are inadequate in many patients. Development of better analgesics is contingent on improved understanding of the molecular mechanisms mediating OA pain. Voltage-gated calcium channels 2.2 (Cav2.2) play a critical role in spinal nociceptive transmission, therefore blocking Cav2.2 activity represents an attractive opportunity for OA pain treatment, but the only available licensed Cav2.2 antagonist ziconitide (PrilatTM) is of limited use. ⋯ Systemic administration of TROX-1 produced a significant inhibition of the mechanical-(vF 8, 26 and 60 g) evoked neuronal responses in MIA rats. TROX-1 did not produce any significant effect on any neuronal measure in Sham controls. Our in vivo electrophysiological results demonstrate a pathological state-dependent effect of TROX-1, which suggests an increased functional role of Cav2, likely Cav2.2, channels in mediating OA pain.