Sheng li xue bao : [Acta physiologica Sinica]
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Neurofibromatosis type 1 (NF1) is a common autosomal dominant disease characterized by formation of multiple benign and malignant tumors. People with this disorder also experience chronic pain, which can be disabling. Neurofibromin, the protein product of the Nf1 gene, is a guanosine triphosphatase activating protein (GAP) for p21Ras (Ras). ⋯ Consistent with that observation, neurons from Nf1+/- mice had lower firing thresholds, lower rheobase currents and shorter firing latencies compared with wildtype neurons. These data clearly demonstrate that GAPs, such as neurofibromin, can alter the excitability of nociceptive sensory neurons. The augmented response of sensory neurons with altered Ras signaling may explain the abnormal pain sensations experienced by people with NF1 and suggests an important role of GAPs in the mechanism of sensory neuron sensitization.
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The present study was conducted to investigate the effect of hepatocyte growth factor (HGF) on cortical neurons exposed to oxygen-glucose deprivation/reperfusion (OGD/R). Primary cultured cerebral cortical neurons were prepared from Sprague-Dawley rats. The cells were used for experiments after culture for 12 d in vitro. ⋯ As detected by semi-quantitative RT-PCR and Western blot analysis, c-Met mRNA and protein were expressed in cerebral cortical neurons cultured for 12 d in vitro. c-Met mRNA and protein expressions in cortical neurons exposed to OGD(2)/R(24) were significantly upregulated and were not affected by pretreatment of HGF at 80 ng/mL. Treatment with c-Met inhibitor SU11274 (5 μmol/L) completely eliminated HGF-mediated protection of cortical neurons subjected to OGD(2)/R(24). The results suggest that HGF directly protects cortical neurons against OGD/R-induced cell injury in a dose-dependent manner, and HGF has a potent anti-apoptotic action on neurons exposed to OGD/R.
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To systematically clarify the effects of apolipoprotein E (aopE) and low-density lipoprotein receptor (LDLR) gene mutant on hyperlipidemia, vascular inflammation impairment and pathogenesis of atherosclerosis (AS), total RNA was isolated from fresh aortas of young apoE/LDLR double knockout (apoE(-/-)/LDLR(-/-)) and wild type (WT) mice using TRIzol reagent. Then RNA was reversely transcribed to first-strand cDNA by reverse transcriptase for reverse transcription polymerase chain reaction (RT-PCR) and real-time RT-PCR. Primer pairs were designed using primer design software according to the gene sequences available in GenBank. β-actin was used as an internal control. ⋯ Primary atherosclerotic lesions were observed in 1-month old apoE(-/-)/LDLR(-/-) mice and were progressing with age. There were no lesions observed in all WT mice at different ages. The data suggest that hyperlipidemia due to apoE and LDLR gene mutant may stimulate the temporal expressions of AS-related genes and contribute to primary atherogenetic lesions and vascular inflammation impairment.
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It is known that stimulation of the α(2A)-adrenoceptors (α(2A)-ARs) by the selective α(2A)-AR agonist guanfacine produces an important and beneficial influence on prefrontal cortical (PFC) cognitive functions such as spatial working memory and selective attention. However, it is unclear whether stimulation of the α(2A)-ARs has a similar effect on fear conditioning that involves the amygdala and hippocampus. ⋯ However, guanfacine produced no effect on acquisition of contextual and auditory fear memories. The present study suggests that beneficial effect of α(2A)-AR stimulation is task-dependent: guanfacine improves spatial learning but not fear conditioning.
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The aim of the present study was to examine whether the thalamic nucleus submedius (Sm) was involved in the modulation of persistent nociception. Using an automated movement detection system to measure nociceptive behavior (agitation) induced by subcutaneous injection of formalin into the hind paw pad, the effects of electrical stimulation or electrolytic lesion of the Sm on the agitation response were examined in conscious rats. ⋯ These results suggest that the Sm is not only involved in the modulation of phase nociception, as reported previously, but also of persistent nociception. The present study provides novel evidence for the participation of the Sm in descending modulation of pain.