目的:初步探讨proBDNF(precursor of brain-derived neurotrophic factor)对海马神经元的可能作用及其机制。方法:采用体外培养胚鼠海马神经元,并给予proBDNF,preBDNF(propeptide of proBDNF)和抗proBDNF血清处理;30min,1h和48h后行尼...目的:初步探讨proBDNF(precursor of brain-derived neurotrophic factor)对海马神经元的可能作用及其机制。方法:采用体外培养胚鼠海马神经元,并给予proBDNF,preBDNF(propeptide of proBDNF)和抗proBDNF血清处理;30min,1h和48h后行尼氏染色,ELK-p(Ets domain protein),ErK2(extracellularsignal regulated kinase)和c-fos免疫细胞化学染色。结果:给予proBDNF处理后,可见培养细胞内ELK-p,ErK2和c-fos表达明显上调,部分细胞核深染;而用抗血清中和内源性proBDNF后,ELK-p、ErK2和c-fos均下调,且细胞出现肿胀、空泡样变化。preBDNF处理组细胞与正常对照组类似。结论:proBDNF可维持海马神经元的存活,其机制可能与激活ErK和ELK信号通路有关。展开更多
Ischemic stroke often elicits profound white matter lesions, which results in poor neurological outcomes and impairing the recovery in post-stroke. However, few studies have focused on white matter lesions caused by c...Ischemic stroke often elicits profound white matter lesions, which results in poor neurological outcomes and impairing the recovery in post-stroke. However, few studies have focused on white matter lesions caused by cerebral ischemia. The present study was aimed to investigate the effects of cornel iridoid glycoside(CIG), a main active component extracted from Cornus officinalis, on the white matter injury induced by ischemic stroke. CIG(60 and 120 mg·kg-1) were administered intragastrically 6 h after middle cerebral artery occlusion reperfusion(MCAO) surgery once a day for 7 d. A series of behavioral tests were carried out to evaluate the neurological function of MCAO rats. White matter structure was detected by luxol fast blue staining and transmission electron microscopy. Immunohistochemical staining was used to assess myelin loss, oligodendrocytes maturation and glial activation. Results showed that CIG remarkably decreased neurological deficit score, accelerated the recovery of somatosensory and motor functions, and ameliorated the memory deficit in MCAO rats. CIG alleviated white matter lesions and demyelination, increased myelin basic protein expression and the number of mature oligodendrocytes in the corpus callosum of MCAO rats. Besides, CIG inhibited the activation of microglia and astrocytes. Further data obtained by western blot analysis indicated that CIG increased the expression of brain-derived neurotrophic factor(BDNF)/p-Trk B, neuregulin-1/Erb B, and PI3 K p110α/p-Akt/p-m TOR in the corpus callosum of MCAO rats. Our findings demonstrated that CIG protected against white matter lesions induced by cerebral ischemia and the mechanisms were partially contributed to increasing BDNF and activating neuregulin-1/Erb B signaling and its downstream PI3 K/Akt/m TOR pathway in white matter.展开更多
Extinction of aversive memories has been a major concern in neuropsychiatric disorders such as anxiety disorders and drug addiction. The ventromedial prefrontal cortex(vmPFC) is important for memory extinction,but the...Extinction of aversive memories has been a major concern in neuropsychiatric disorders such as anxiety disorders and drug addiction. The ventromedial prefrontal cortex(vmPFC) is important for memory extinction,but the underlying mechanisms are little known. Here,we report that extinction of conditioned place aversion(CPA),a type of aversive memory associated with drug withdrawal,required activation of Rho GTPase Rac1 in the vmPFC in a brain-derived neurotrophic factor(BDNF)-dependent manner,which triggers actin polymerization via Pak1-cofilin signaling pathway,leading to synaptic localization of activity-regulated cytoskeleton-associated protein(Arc) in the vmPFC. The synaptic Arc further determines GABA_Areceptor(GABA_AR) endocytosis that is necessary and sufficient for vmP FC long-term potentiation and CPA extinction. Thus,extinction of an aversive memory associated with drug withdrawal is intriguingly controlled by Rac1-dependent GABA_AR endocytosis in the vmPFC,thereby suggesting therapeutic targets to promote extinction of the unwanted memory.展开更多
文摘Ischemic stroke often elicits profound white matter lesions, which results in poor neurological outcomes and impairing the recovery in post-stroke. However, few studies have focused on white matter lesions caused by cerebral ischemia. The present study was aimed to investigate the effects of cornel iridoid glycoside(CIG), a main active component extracted from Cornus officinalis, on the white matter injury induced by ischemic stroke. CIG(60 and 120 mg·kg-1) were administered intragastrically 6 h after middle cerebral artery occlusion reperfusion(MCAO) surgery once a day for 7 d. A series of behavioral tests were carried out to evaluate the neurological function of MCAO rats. White matter structure was detected by luxol fast blue staining and transmission electron microscopy. Immunohistochemical staining was used to assess myelin loss, oligodendrocytes maturation and glial activation. Results showed that CIG remarkably decreased neurological deficit score, accelerated the recovery of somatosensory and motor functions, and ameliorated the memory deficit in MCAO rats. CIG alleviated white matter lesions and demyelination, increased myelin basic protein expression and the number of mature oligodendrocytes in the corpus callosum of MCAO rats. Besides, CIG inhibited the activation of microglia and astrocytes. Further data obtained by western blot analysis indicated that CIG increased the expression of brain-derived neurotrophic factor(BDNF)/p-Trk B, neuregulin-1/Erb B, and PI3 K p110α/p-Akt/p-m TOR in the corpus callosum of MCAO rats. Our findings demonstrated that CIG protected against white matter lesions induced by cerebral ischemia and the mechanisms were partially contributed to increasing BDNF and activating neuregulin-1/Erb B signaling and its downstream PI3 K/Akt/m TOR pathway in white matter.
文摘Extinction of aversive memories has been a major concern in neuropsychiatric disorders such as anxiety disorders and drug addiction. The ventromedial prefrontal cortex(vmPFC) is important for memory extinction,but the underlying mechanisms are little known. Here,we report that extinction of conditioned place aversion(CPA),a type of aversive memory associated with drug withdrawal,required activation of Rho GTPase Rac1 in the vmPFC in a brain-derived neurotrophic factor(BDNF)-dependent manner,which triggers actin polymerization via Pak1-cofilin signaling pathway,leading to synaptic localization of activity-regulated cytoskeleton-associated protein(Arc) in the vmPFC. The synaptic Arc further determines GABA_Areceptor(GABA_AR) endocytosis that is necessary and sufficient for vmP FC long-term potentiation and CPA extinction. Thus,extinction of an aversive memory associated with drug withdrawal is intriguingly controlled by Rac1-dependent GABA_AR endocytosis in the vmPFC,thereby suggesting therapeutic targets to promote extinction of the unwanted memory.
