Journal of neurochemistry
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Journal of neurochemistry · Feb 2009
Fibronectin stimulates TRPV1 translocation in primary sensory neurons.
Extracellular matrix (ECM) molecules are highly variable in their composition and receptor recognition. Their ubiquitous expression profile has been linked to roles in cell growth, differentiation, and survival. Recent work has identified certain ECM molecules that serve as dynamic signal modulators, versus the more-recognized role of chronic modulation of signal transduction. ⋯ This FN-induced increase in TRPV1 sensitivity to activation is coupled by an increase in plasma membrane expression of TRPV1, as well as an increase in tyrosine phosphorylation of TRPV1 in TG neurons. Furthermore, TG neurons cultured on FN demonstrated an increase in capsaicin-mediated Ca(2+) accumulation relative to neurons cultured on poly-D-lysine. Data presented from these studies indicate that FN stimulates tyrosine-phosphorylation-dependent translocation of the TRPV1 receptor to the plasma membrane, identifying FN as a critical component of the ECM capable of sensory neuron sensitization.
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Journal of neurochemistry · Feb 2009
CREB activation in the rapid, intermediate, and delayed ischemic preconditioning against hypoxic-ischemia in neonatal rat.
Ischemic preconditioning (IP) is a defense program in which exposure to sublethal ischemia followed by a period of reperfusion results in subsequent resistance to severe ischemic insults. Very few in vivo IP models have been established for neonatal brain. We examined whether rapid, intermediate, and delayed IP against hypoxic-ischemia (HI) could be induced in neonatal brain, and if so, whether the IP involved phosphorylation of cAMP response element-binding protein (pCREB) after HI. ⋯ The increases of caspase-3 and calpain-mediated proteolysis of a-spectrin post-HI were significantly reduced only in 22-h IP group. Furthermore, all three IP groups had long-term neuroprotection at behavioral and pathological levels compared with no-IP group. In conclusion, IP, rapid, intermediate, or delayed, in neonatal rat brain activates CREB, up-regulates Bcl-2, induces extensive brakes on caspase-dependent and -independent apoptosis after HI, and provides long-term neuroprotection.
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Journal of neurochemistry · Jan 2009
The glutamatergic nature of TRPV1-expressing neurons in the spinal dorsal horn.
The transient receptor potential vanilloid receptor 1 (TRPV1) is expressed on primary afferent terminals and spinal dorsal horn neurons. However, the neurochemical phenotypes and functions of TRPV1-expressing post-synaptic neurons in the spinal cord are not clear. In this study, we tested the hypothesis that TRPV1-expressing dorsal horn neurons are glutamatergic. ⋯ However, capsaicin had no effect on GABAergic and glycinergic spontaneous inhibitory post-synaptic currents of lamina II neurons in RTX-treated or dorsal rhizotomized rats. Collectively, our study provides new histological and functional evidence that TRPV1-expressing dorsal horn neurons in the spinal cord are glutamatergic and that they mediate excitatory synaptic transmission. This finding is important to our understanding of the circuitry and phenotypes of intrinsic dorsal horn neurons in the spinal cord.
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Journal of neurochemistry · Dec 2008
Protective effects of astaxanthin on 6-hydroxydopamine-induced apoptosis in human neuroblastoma SH-SY5Y cells.
Parkinson's disease (PD) is a neurodegenerative disorder characterized by selective loss of dopaminergic neurons in the substantia nigra pars compacta. Although understanding of the pathogenesis of PD remains incomplete, increasing evidence from human and animal studies has suggested that oxidative stress is an important mediator in its pathogenesis. Astaxanthin (Asx), a potent antioxidant, has been thought to provide health benefits by decreasing the risk of oxidative stress-related diseases. ⋯ Pharmacological approaches showed that the activation of p38 MAPK has a critical role in 6-OHDA-induced mitochondrial dysfunctions and apoptosis. Furthermore, Asx markedly abolished 6-OHDA-induced reactive oxygen species generation, which resulted in the blockade of p38 MAPK activation and apoptosis induced by 6-OHDA treatment. Taken together, the present results indicated that the protective effects of Asx on apoptosis in SH-SY5Y cells may be, at least in part, attributable to the its potent antioxidative ability.
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Journal of neurochemistry · Dec 2008
The antipsychotic spiperone attenuates inflammatory response in cultured microglia via the reduction of proinflammatory cytokine expression and nitric oxide production.
Glial activation and neuroinflammatory processes play an important role in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and HIV dementia. Activated glia cells can secrete various proinflammatory cytokines and neurotoxic mediators, which may influence neuronal cell survival. Recent studies have demonstrated that glia cell-mediated neuroinflammation is also related to the pathophysiology of schizophrenia. ⋯ Spiperone inhibited nuclear translocation and DNA binding of the p65 subunit of nuclear factor kappa B (NF-kappaB), inhibitor of kappa B (IkappaB) degradation, and phosphorylation of p38 mitogen-activated protein kinase in the lipopolysaccharide-stimulated BV-2 microglia cells. Moreover, spiperone was neuroprotective, as the drug reduced microglia-mediated neuroblastoma cell death in the microglia/neuron co-culture. These results imply that the antipsychotic spiperone has anti-inflammatory and neuroprotective effects in the central nervous system by modulating glial activation.