Neuroscience
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Bone pain is one of the most common complications in cancer patients with bone metastases, and has the most significant impact on quality of life for patients. Patients with bone cancer pain may be difficult to treat due to the poor understanding of the mechanisms; therefore, the mechanisms of bone cancer pain required elucidation for developing new therapeutics. Recent studies show that SCN7A/Nax channel serves as a sodium-level sensor of the body fluid that controls the Na-intake behavior by changing the excitability of neurons. ⋯ These electrophysiological changes of neurons increased ectopic spike discharge which was thought to be an important generator of chronic pain, however, the hyperexcitability was completely reversed by SCN7A/Nax knockdown. These results demonstrate that enhanced expression of SCN7A/Nax channel within distinct subpopulation of DRG neurons contributes to bone cancer pain by increasing the excitability of these neurons. These findings may lead to novel strategies for the treatment of bone cancer pain.
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Nuclear factor-erythroid 2-related factor-2 (Nrf2) mediated regulation of cellular antioxidant production and the anti-inflammatory mechanism play an important role in neuroprotection against neurodegenerative diseases. Naringin a citrus flavonone, has been reported to possess neuroprotective effect against Huntington's disease, and other neurodegenerative disorders, however the mechanisms underlying its beneficial effects on 3-nitropropionic acid (3-NP)-induced neurodegeneration are poorly defined. The objective of the present study was to investigate the neuroprotective role of naringin and delineate the mechanism of action on 3-NP-induced neurodegeneration. ⋯ Nissl staining and transmission electron microscopic studies showed that naringin modulated 3-NP-induced histological changes. Naringin induces NAD(P)H:quinone oxidoreductase-1, heme oxygenase-1, glutathione S-transferase P1 and gamma-glutamylcysteine ligase mRNA expressions through the activation of Nrf2 and decreased the expressions of pro-inflammatory mediators like tumour necrosis factor-alpha, cyclooxygenase-2 and inducible nitric oxide synthase. These results indicate that naringin might be beneficial in mitigating 3-NP-induced neurodegeneration through the enhancement of phase II and antioxidant gene expressions via Nrf2 activation; thereby modulating the oxidative stress and inflammatory responses.
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The effect of physical training on the neurochemical and oxidative stress markers were evaluated in the striatum of rats with Parkinson's disease (PD). Untrained+sham-operated (USO), untrained+PD (UPD), trained+sham-operated (TSO), and trained+PD (TPD) were submitted to training on the treadmill. The PD was induced and 7 days after the lesion, the animals underwent a rotational test and euthanasia by decapitation. ⋯ The UPD and TPD groups showed a clear rotational asymmetry, apart from a significant reduction in the level of TH, BDNF, α-synuclein, SOD, CAT, and GPX as well as an increase in the TBARS and carbonyl content, as observed in the UPD group. The TH level was not significantly altered but the TPD group increased the levels of BNDF, SERCA II, SOD, and CAT and decreased the oxidative damage in lipids and protein. The effects of exercise on PD indicate the possibility that exercise, to a certain extent, modulates neurochemical status in the striatum of rats, possibly by improving the oxidative stress parameters.
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The endocannabinoid system is crucially involved in the regulation of brain activity and inflammation. We have investigated the localization of cannabinoid CB1 and CB2 receptors in adult rat brains before and after focal cerebral ischemia due to endothelin-induced transient occlusion of the middle cerebral artery (eMCAO). Using immunohistochemistry, both receptor subtypes were identified in cortical neurons. ⋯ KN38-7271 remained effective, even if its application was delayed up to 6h post eMCAO. Finally, we show that the endocannabinoid system assembles a comprehensive machinery to defend the brain against the devastating consequences of cerebral ischemia. In summary, this study underlines the therapeutic potential of CB1 and/or CB2 receptor agonists against neurodegenerative diseases or injuries involving acute or chronic imbalances of cerebral blood flow and energy consumption.
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Children with type 1 diabetes mellitus (DM) are at risk of developing cognitive difficulties. Although a diabetes onset of patient influences cognitive difficulties, synaptic properties related to the age of diabetes onset remain unknown. ⋯ Furthermore, impaired LTD of juvenile-onset STZ-rats was restored with an NMDA receptor antagonist. These results suggest that the pathophysiology of diabetes-induced cognitive difficulties varies with the age of diabetes onset.