Journal of neurochemistry
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Journal of neurochemistry · May 2011
Na-K-Cl cotransporter-1 in the mechanism of cell swelling in cultured astrocytes after fluid percussion injury.
Brain edema and associated increased intracranial pressure are major consequences of traumatic brain injury (TBI). An important early component of the edema associated with TBI is astrocyte swelling (cytotoxic edema). Mechanisms for such swelling, however, are poorly understood. ⋯ Bumetanide, an inhibitor of NKCC1, significantly reduced the trauma-induced astrocyte swelling (61%). Silencing NKCC1 with siRNA led to a reduction in trauma-induced NKCC1 activity as well as in cell swelling. These findings demonstrate the critical involvement of NKCC1 in the astrocyte swelling following in vitro trauma, and suggest that blocking NKCC1 activity may represent a useful therapeutic strategy for the cytotoxic brain edema associated with the early phase of TBI.
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Journal of neurochemistry · May 2011
Resveratrol prevents alcohol-induced cognitive deficits and brain damage by blocking inflammatory signaling and cell death cascade in neonatal rat brain.
Human prenatal ethanol exposure that occurs during a period of increased synaptogenesis known as the 'brain growth spurt' has been associated with significant impairments in attention, learning and memory. Recent studies have shown that administration of ethanol to infant rats during the synaptogenesis period (first 2 weeks after birth) triggers extensive apoptotic neurodegeneration throughout many regions of the developing brain and results in cognitive dysfunctions as the animal matures. The present study was designed with an aim to investigate the effect of resveratrol, a polyphenolic phytoalexin (trans-3,5,4-trihydroxy stilbene) present in red wine on alcohol-induced cognitive deficits and neuronal apoptosis in rat pups postnatally exposed to ethanol. ⋯ Behavioral deficit in ethanol-exposed pups was associated with enhanced acetylcholinesterase activity, increased oxidative-nitrosative stress, cytokine (TNF-α, IL-1β and TGF-β), nuclear factor kappa beta and caspase 3 levels in both cerebral cortex and hippocampus. Chronic treatment with resveratrol (10 and 20 mg/kg) significantly attenuated all the behavioral, biochemical and molecular changes in different brain regions of ethanol administered pups. The major finding of the study is that resveratrol blocks activation of nuclear factor kappa beta pathway and apoptotic signaling and prevents cognitive deficits in rats postnatally exposed to ethanol.
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Journal of neurochemistry · Mar 2011
Dramatic increase in readthrough acetylcholinesterase in a cellular model of oxidative stress.
Moderate, transient oxidative stress is achieved in SH-SY5Y cells using tertiary butylhydroperoxide as oxidant. Over a recovery period of 24 h, the enzymatic activity and protein levels of the acetylcholinesterase (AChE) splice variants tailed AChE (AChE-T) and readthrough AChE (AChE-R) are monitored. Their time-dependent correlation to pro- and anti-apoptotic factors, namely caspase 3 and Bcl-2, respectively, as well as lactate dehydrogenase release as a measure of cell viability is assessed. ⋯ In contrast, AChE-R rises continuously during the recovery period, reaching peak intracellular levels that are up to six times higher than control levels 3-4 h post-stress, and is released from cells in substantial amounts. Moreover, anti-apoptotic Bcl-2 increases significantly, peaking 2-3 h after this AChE-R peak has occurred. We believe this study presents the first work that demonstrates - without relying on techniques of over-expression - the time-dependent correlation between apoptotic processes and related rescue mechanisms involving AChE isoforms in a neuronal cell line.
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Journal of neurochemistry · Jan 2011
Comparative StudycAMP-dependent protein kinase activated Fyn in spinal dorsal horn to regulate NMDA receptor function during inflammatory pain.
Selective inhibition of GluN2B-containing NMDA receptor (GluN2BR) in spinal dorsal horn effectively alleviates inflammatory pain, suggesting the up-regulation of GluN2BR function involved in central sensitization. Previous studies have demonstrated that the increase in GluN2BR synaptic expression serves as a key step to enhance GluN2BR function after intradermal injection of Complete Freund's Adjuvant (CFA). Here, we showed that cAMP-dependent protein kinase (PKA) played an important role in redistributing GluN2BR at synapses, because inhibition of PKA activity impaired GluN2BR accumulation at post-synaptic density (PSD)-enriched fraction in CFA-injected mice, and direct stimulation of PKA in naïve mice mimicked the effect of CFA by recruiting GluN2BR at PSD fraction to evoke pain sensitization. ⋯ The active Fyn then promoted GluN2B phosphorylation at Tyr1472, a molecular event known to prevent GluN2BR endocytosis. As a result, pharmacological or genetic manipulation of Fyn activity greatly depressed GluN2BR accumulation at PSD-enriched fraction and ameliorated mechanical allodynia induced by PKA. Our data thus elucidated a critical role of PKA/Fyn/GluN2B signaling in triggering GluN2BR hyperfunction and pain hypersensitivity.
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Journal of neurochemistry · Dec 2010
Regulation of ryanodine receptors by dopamine D1 receptors during methamphetamine-induced place conditioning.
Little is known about ryanodine receptors (RyRs) related to the methamphetamine (METH)-induced place preference. The present study was designed to ascertain whether RyRs could play a role in the development of METH-induced place preference in the mouse. The METH-induced place preference was dose-dependently suppressed by dantrolene, a RyRs receptor antagonist. ⋯ Both the dopamine D(1) receptor antagonist SCH23390 and the dopamine D(2) receptor antagonist sulpiride inhibited the development of METH-induced place conditioning. In contrast, the increases of RyRs 1 and 2 in the frontal cortex and of RyRs 1 in the limbic forebrain were completely abolished by SCH23390, whereas sulpiride had no effect. These findings indicate that up-regulation of RyRs is regulated through the activation of dopamine D(1) receptors in the METH-conditioning.