Neurochemical research
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Neurochemical research · Aug 2011
Mechanism of CaM kinase IV activation during hypoxia in neuronal nuclei of the cerebral cortex of newborn piglets: the role of Src kinase.
The present study aims to investigate the mechanism of CaM kinase IV activation during hypoxia and tests the hypothesis that hypoxia-induced increased activity of CaM kinase IV is due to Src kinase mediated increased tyrosine phosphorylation of calmodulin and CaM kinase IV in neuronal nuclei of the cerebral cortex of newborn piglets. Piglets were divided into normoxic (Nx, n = 5), hypoxic (Hx, F(i)O(2) of 0.07 for 1 h, n = 5) and hypoxic-pretreated with Src kinase inhibitor PP2 (Hx-Srci, n = 5) groups. Src inhibitor was administered (1.0 mg/kg, I. ⋯ We conclude that the mechanism of hypoxia-induced increased activation of CaM kinase IV is mediated by Src kinase-dependent tyrosine phosphorylation of the enzyme and its activator calmodulin. We propose that Tyr(99) phosphorylated calmodulin, as compared to non-phosphorylated, binds with a higher affinity at the calmodulin binding site (rich in basic amino acids) of CaM kinase IV leading to increased activation of CaM kinase IV. Similarly, tyrosine phosphorylated CaM kinase IV binds its substrate with a higher affinity and thus increased tyrosine phosphorylation leads to increased activation of CaM kinase IV resulting in increased CREB phosphorylation that triggers increased transcription of proapoptotic proteins that initiate hypoxic neuronal death.
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Neurochemical research · Aug 2011
Protective effect of lycopene on oxidative stress and cognitive decline in rotenone induced model of Parkinson's disease.
Evidence from clinical and experimental studies indicate that oxidative stress is involved in pathogenesis of Parkinson's disease. The present study was designed to investigate the neuroprotective potential of lycopene on oxidative stress and neurobehavioral abnormalities in rotenone induced PD. Rats were treated with rotenone (3 mg/kg body weight, intraperitoneally) for 30 days. ⋯ Lycopene treatment also prevented release of cytochrome c from mitochondria. Collectively, these observations suggest that lycopene supplementation along with rotenone for 30 days prevented rotenone-induced alterations in antioxidants along with the prevention of rotenone induced oxidative stress and neurobehavioral deficits. The results provide an evidence for beneficial effect of lycopene supplementation in rotenone-induced PD and suggest therapeutic potential in neurodegenerative diseases involving accentuated oxidative stress.
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Neurochemical research · May 2011
Upregulation of inflammatory mediators in a model of chronic pain after spinal cord injury.
Chronic neuropathic pain is a disabling condition observed in large number of individuals following spinal cord injury (SCI). Recent progress points to an important role of neuroinflammation in the pathogenesis of central neuropathic pain. The focus of the present study is to investigate the role of proinflammatory molecules IL-1β, TNF-α, MCP-1, MMP-9 and TIMP-1 in chronic neuropathic pain in a rodent model of SCI. ⋯ Changes in expression of mRNAs for IL-1β, TNF-α, MCP-1, MMP-9 and TIMP-1 were assessed using real-time polymerase chain reaction in spinal cord including the injury epicenter along with regions above and below the level of lesion at day 28 post-injury. A significant increase was observed in the expression of MCP-1, TNF-α, TIMP-1 and IL-1β in the injury epicenter, whereas only TIMP-1 was upregulated in the area below the injury epicenter. The results of the study suggest that prolonged upregulation of inflammatory mediators might be involved in chronic neuropathic pain in SCI, and that TIMP-1 may play a role in maintenance of chronic below level pain.
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Neurochemical research · Feb 2011
Alterations in inflammatory mediators, oxidative stress parameters and energetic metabolism in the brain of sepsis survivor rats.
Sepsis is characterized by biochemical alterations in the central nervous system at early times and cognitive impairment at late times after induction in sepsis animal model. In order to understand at least in part the mechanism of disease, we have evaluated the effects of sepsis on cytokine levels in the cerebrospinal fluid (CSF); oxidative parameters; the activity of the electron transport chain enzymes; and creatine kinase (CK) activity in the brain of sepsis survivor rats 10 days after cecal ligation and perforation (CLP). Male Wistar rats underwent CLP with "basic support" or sham-operated. ⋯ Oxidative stress and mitochondrial alterations observed during early times in sepsis, persisted up to 10 days after surgery. The cytokines levels during the early times were found at high levels, decreasing to low levels after 10 days. In conclusion, these findings may contribute for a better comprehension of the cognitive damage in sepsis survivor rats.
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Neurochemical research · Jan 2011
Differential roles of phosphorylated AMPA receptor GluR1 subunits at Serine-831 and Serine-845 sites in spinal cord dorsal horn in a rat model of post-operative pain.
Previous studies have demonstrated that the enhanced levels of phosphorylated α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor GluR1 subunits at Serine-831 (pGluR1-Ser-831) and Serine-845 (pGluR1-Ser-845) in the spinal cord dorsal horn are involved in central sensitization of inflammatory pain. However, whether the phosphorylatory regulation of AMPA receptor GluR1 subunits is implicated in the development and maintenance of post-operative pain remains unclear. The current study aims to examine the functional regulation of AMPA receptor GluR1 subunit through its phosphorylation mechanism during the period of post-operative painful events in rats. ⋯ Intrathecal injection of a calcium-dependent protein kinase (PKC) inhibitor, Gö6983 (10 μM), significantly reversed the incision-mediated over-expression of pGluR1-Ser-831 in spinal dorsal horn at 3 h after incision and decreased the cumulative pain scores as well. These results indicate that the phosphorylation of GluR1 subunits at Serine-831 and Serine-845 sites might be differentially regulated following surgical procedures and support a neurobiological mechanism of post-operative pain involved in phosphorylation of AMPA subunits GluR1-Ser-831, but not pGluR1-Ser-845. Our study suggests that the therapeutic targeting the phosphorylation regulation of AMPA receptor GluR1 subunit at Serine-831 site would be potentially significant for treating postoperative pain.