Molecular neurobiology
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Molecular neurobiology · Aug 2016
Hypericum perforatum Attenuates Spinal Cord Injury-Induced Oxidative Stress and Apoptosis in the Dorsal Root Ganglion of Rats: Involvement of TRPM2 and TRPV1 Channels.
Oxidative stress and cytosolic Ca(2+) overload have important roles on apoptosis in dorsal root ganglion (DRG) neurons after spinal cord injury (SCI). Hypericum perforatum (HP) has an antioxidant property in the DRGs due to its ability to modulate NADPH oxidase and protein kinase C pathways. We aimed to investigate the protective property of HP on oxidative stress, apoptosis, and Ca(2+) entry through transient receptor potential melastatin 2 (TRPM2) and transient receptor potential vanilloid 1 (TRPV1) channels in SCI-induced DRG neurons of rats. ⋯ Mitochondria were reported to accumulate Ca(2+), provided intracellular Ca(2+) rises, thereby leading to depolarization of mitochondrial membranes and release of apoptosis-inducing factors such as caspase 3 and caspase 9. HP via regulation of NADPH oxidase and PKC inhibits TRPM2 and TRPV1 channels. The molecular pathway may be a cause of SCI-induced pain and neuronal death, and the subject should be urgently investigated.
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Molecular neurobiology · Aug 2016
Interleukin-17A Acts to Maintain Neuropathic Pain Through Activation of CaMKII/CREB Signaling in Spinal Neurons.
Immunity and neuroinflammation play major roles in neuropathic pain. Spinal interleukin (IL)-17A, as a mediator connecting innate and adaptive immunity, has been shown to be an important cytokine in neuroinflammation and acute neuropathic pain. However, the effects and underlying mechanisms of spinal IL-17A in the maintenance of neuropathic pain remain unknown. ⋯ Furthermore, we showed that blocking CaMKII with KN93 significantly reduced SNL- or rIL-17A-induced hyperalgesia and p-CREB expression. Our in vitro data showed that KN93 also significantly inhibited rIL-17A-induced CREB activation in primary cultured spinal neurons. Taken together, our study indicates that astrocytic IL-17A plays important roles in the maintenance of neuropathic pain through CaMKII/CREB signaling pathway in spinal cord, and thus targeting IL-17A may offer an attractive strategy for the treatment of chronic persistent neuropathic pain.
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Molecular neurobiology · Aug 2016
BDNF Induces Striatal-Enriched Protein Tyrosine Phosphatase 61 Degradation Through the Proteasome.
Brain-derived neurotrophic factor (BDNF) promotes synaptic strengthening through the regulation of kinase and phosphatase activity. Conversely, striatal-enriched protein tyrosine phosphatase (STEP) opposes synaptic strengthening through inactivation or internalization of signaling molecules. Here, we investigated whether BDNF regulates STEP levels/activity. ⋯ BDNF also promoted UPS-mediated STEP61 degradation in cultured striatal and hippocampal neurons. In contrast, nerve growth factor and neurotrophin-3 had no effect on STEP61 levels. Our results thus indicate that STEP61 degradation is an important event in BDNF-mediated effects.