Neuropharmacology
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This study analyzed and compared the effects of EGCG treatment on the expression of NTFs and NTF receptors expression in the sciatic nerve and the L3-L6 spinal cord segments at the early phase of regeneration following sciatic nerve crush injury. Analysis of BDNF, GDNF and NT3 neurotropic factors and Trk-B, Trk-C and NGFR-p75 receptors in neurons in the spinal cord of CRUSH and CRUSH + EGGC rats showed significant (p < 0.0001) decrease compared to NAÏVE and SHAM at day 1, 3, 7 and 14 after nerve injury. EGCG treatment significantly (p < 0.0001) increased the BDNF, GDN, NT3, Trk-B, Trk-C and NGFR-p75 immunostaining in the L3-L6 spinal cord compared to CRUSH animals. ⋯ EGCG treatment significantly (p < 0.0001) increased the Trk-B, Trk-C and NGFR-p75 mRNA gene expressions in the sciatic nerves compared to CRUSH group. Only at day 1, CRUSH + EGCG animals displayed significant rise in the sciatic nerves NT3 gene expression compared to CRUSH group. Our data suggest that the EGCG neuroprotective effect on the spinal cord neurons may be mediated through the modulation of NTFs and NTF receptors following nerve crush injury in a rat model.
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Cannabinoid (CB) agonists suppress nausea in humans and animal models; yet, their underlying neural substrates remain largely unknown. Evidence suggests that the visceral insular cortex (VIC) plays a critical role in nausea. Given the expression of CB1 receptors and the presence of endocannabinoids in this brain region, we hypothesized that the VIC endocannabinoid system regulates nausea. ⋯ Inhibition of MAGL robustly increased 2-AG in the VIC, while FAAH inhibition had no effect on AEA. Finally, we demonstrated that inhibition of MAGL reduced VIC Fos immunoreactivity in response to LiCl treatment. Taken together, these findings provide compelling evidence that acute nausea selectively increases 2-AG in the VIC, and suggests that 2-AG signaling within the VIC regulates nausea by reducing neuronal activity in this forebrain region.