Neurochemical research
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Neurochemical research · Sep 2012
Oxidative stress induced NMDA receptor alteration leads to spatial memory deficits in temporal lobe epilepsy: ameliorative effects of Withania somnifera and Withanolide A.
In the present study we investigate the effect of Withania somnifera (WS) root extract and Withanolide A (WA) in restoring spatial memory deficit by inhibiting oxidative stress induced alteration in glutamergic neurotransmission. We demonstrate significant cellular loss in hippocampus of epileptic rats, visualized through decreased TOPRO stained neurons. Impaired spatial memory was observed in epileptic rats after Radial arm maze test. ⋯ The treatment with WS and WA resulted in physiological expression of NMDA receptors. This data suggests that oxidative stress effects membrane constitution resulting in decreased NMDA receptor density leading to impaired spatial memory. Treatment with WS and WA has ameliorated spatial memory deficits by enhancing antioxidant system and restoring altered NMDA receptor density.
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Neurochemical research · Aug 2012
Interleukin-10 of red nucleus plays anti-allodynia effect in neuropathic pain rats with spared nerve injury.
Our previous studies have shown that pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) in red nucleus (RN) are involved in the development of neuropathic pain and play facilitated roles on the mechanical allodynia induced by peripheral nerve injury. The current study was designed to evaluate the expression and effect of IL-10, an anti-inflammatory cytokine, in the RN of rats with spared nerve injury (SNI). ⋯ Results demonstrated that higher doses of IL-10 (1.0 and 0.5 μg/μl) significantly attenuated the mechanical allodynia of neuropathic rats, while 0.1 μg/μl of IL-10 did not show any analgesic effect. These results suggest that IL-10 of RN participates in the development of neuropathic pain and plays inhibitory roles on the mechanical allodynia induced by SNI.
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Neurochemical research · May 2012
Protective effects of mGluR5 positive modulators against traumatic neuronal injury through PKC-dependent activation of MEK/ERK pathway.
Several previous studies utilizing selective pharmacological antagonists have demonstrated that type 5 metabotropic glutamate receptors (mGluR5) are potential therapeutic targets for the treatment of numerous disorders of the central nervous system, but the role of mGluR5 activation in traumatic brain injury (TBI) is not fully understood. Here in an in vitro TBI model, the mGluR5 agonist (RS)-2-chloro-5- hydroxyphenylglycine (CHPG) and the positive allosteric modulators 3-cyano-N-(1,3- diphenyl-1H-pyrazol-5-yl) benzamide (CDPPB) were used to investigate the neuroprotective potency of mGluR5 activation. Data showed that CHPG and CDPPB suppressed the increase of LDH release and caspase-3 activation induced by traumatic neuronal injury in a dose-dependent manner, and the salutary effects were also present when these compounds were added 1 h after injury. ⋯ With the pretreatment of chelerythrine chloride, a PKC inhibitor, the surpressing effects of CHPG and CDPPB on traumatic injury-evoked LDH release and caspase-3 activation were blocked. All of these findings extended the protective role of mGluR5 activation in an in vitro model of TBI and suggested that these protective effects might be mediated by the PKC-dependent activation of MEK/ERK pathway. These results may have important implications for the development of mGluR5 modulators to treat TBI.
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Neurochemical research · Apr 2012
ReviewTricyclodecan-9-yl-xanthogenate (D609) mechanism of actions: a mini-review of literature.
Tricyclodecan-9-yl-xanthogenate (D609) is known for its antiviral and antitumor properties. D609 actions are widely attributed to inhibiting phosphatidylcholine (PC)-specific phospholipase C (PC-PLC). D609 also inhibits sphingomyelin synthase (SMS). ⋯ D609 showed promise in cancer studies, reduced atherosclerotic plaques (inhibition of PC-PLC) and cerebral infarction after stroke (PC-PLC or SMS). D609 actions as an antagonist to pro-inflammatory cytokines have been attributed to PC-PLC. The purpose of this review is to comprehensively evaluate the literature and summarize the findings and relevance to cell cycle and CNS pathologies.
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Neurochemical research · Apr 2012
Comparative StudyTenuigenin promotes proliferation and differentiation of hippocampal neural stem cells.
The present study was to investigate the influence of tenuigenin, an active ingredient of Polygala tenuifolia Willd, on the proliferation and differentiation of hippocampal neural stem cells in vitro. Tenuigenin was added to a neurosphere culture and neurosphere growth was measured using MTT assay. The influence of tenuigenin on the proliferation of neural progenitors was examined by Clone forming assay and BrdU detection. ⋯ More neurons were also obtained when tenuigenin was added in the differentiation medium. These findings suggest that tenuigenin is involved in regulating the proliferation and differentiation of hippocampal neural stem cells. This result may be one of the underlying reasons for tenuigenin's nootropic and anti-aging effects.