海马γ振荡细胞内信号机制的探讨
发布时间：2019-03-28 10:44
【摘要】：背景γ振荡是神经网络功能的一个特征,存在于多个脑区,主要由脑网络中的抑制性中间神经元及兴奋性锥体细胞相互作用产生,在注意力高度集中、探索行为及学习记忆活动中明显增强,因此,γ振荡反映了脑的高级功能,并被广泛应用于学习和记忆功能相关机制的研究。而神经退行性疾病,如阿尔茨海默病(Alzheimer’s disease,AD)及精神类疾病,如精神分裂症患者的γ振荡受损。最近的研究发现γ频率的光刺激减少了AD模型鼠海马Aβ的产生。细胞内信号分子及激酶,如AC/PKA、PI3/Akt(PKB)、PKC及AMPK、HDAC等在突触传递及突触可塑性中起重要作用,但其是否参与调节γ振荡并不清楚。我们的研究旨在探讨这些细胞内信号分子及激酶对γ振荡的调控作用,以了解γ振荡的可调控因素及对学习记忆功能受损相关的临床疾病提供新的科研思路和治疗靶点。目的探讨细胞内信号分子及激酶对大鼠海马γ振荡的影响及调控机制。方法1细胞外场电位记录γ振荡实验对象为4~6周的雄性SD大鼠,用10%水合氯醛麻醉成功后,抽取0℃的切片脑脊液经左心室系统灌流至四肢变白后,快速断头取脑并固定,用振动切片机将脑组织水平切成350μm厚的脑片。然后将含有海马结构的脑片迅速转移到孵育槽上孵育60分钟后,用红藻氨酸受体激动剂(Kainate,KA)可诱导出稳定持久的γ频率振荡。实验采用细胞外微电极方式记录电活动。2观察细胞内信号分子及激酶抑制剂对γ振荡功率谱及峰值频率的影响。3统计分析用SPike 2软件对数据进行离线分析,实验数据使用Sigmastat软件统计。实验结果以平均值±标准差来表示。如果P0.05,则被认为其具有统计学意义。结果1 AC抑制剂MDLL-12330A(MDL),PKA抑制剂H89,ERK抑制剂U0126及PKC抑制剂G6983对海马KA诱导的γ振荡无明显影响。2 PI3K抑制剂wortmannin对γ振荡无明显作用,而Akt抑制剂TCBN增加了海马γ振荡的能谱(P0.05)。3 AMPK抑制剂CC增加了海马γ振荡的能谱(P0.01)。4非特异性HDAC抑制剂SAHA增加了KA诱导的γ振荡的能谱(P0.001),选择性HDAC抑制剂PD106和HDAC6抑制剂NXT也增加了γ振荡的能谱(P0.05)。结论海马KA诱导的γ振荡存在Akt、HDAC、AMPK的激活,而这种激活对γ振荡存在负性调节作用,这种负性调节作用提示γ振荡存在自稳态调节机制。AC、PKA、ERK、PI3K、PKC不参与海马KA诱导的γ振荡。
[Abstract]:Background 纬 oscillation is a characteristic of neural network function. It exists in many brain regions. It is mainly produced by the interaction of inhibitory intermediate neurons and excitatory pyramidal cells in the brain network. Therefore, 纬-oscillations reflect the advanced functions of the brain and have been widely used in the study of the related mechanisms of learning and memory functions. Neurodegenerative diseases, such as Alzheimer's disease (Alzheimer's disease,AD) and psychotic diseases, such as schizophrenia, suffer from impaired gamma oscillations. Recent studies have found that light stimulation at 纬-frequency reduces the production of A 尾 in hippocampus of AD model rats. Intracellular signal molecules and kinases, such as AC/PKA,PI3/Akt (PKB), PKC and AMPK,HDAC, play an important role in synaptic transmission and synaptic plasticity. Our research aims to explore the regulatory effects of these intracellular signal molecules and kinases on 纬 oscillation in order to understand the regulatory factors of 纬 oscillation and to provide new research ideas and therapeutic targets for clinical diseases related to learning and memory impairment. Objective to investigate the effects of intracellular signal molecules and kinases on rat hippocampal 纬 oscillation and its regulatory mechanism. Methods 1Cellular field potential recording 纬-oscillations in male SD rats for 6 weeks were studied. After anesthesia with 10% chloral hydrate, the cerebrospinal fluid (CSF) at 0 鈩，
本文编号：2448790
[Abstract]:Background 纬 oscillation is a characteristic of neural network function. It exists in many brain regions. It is mainly produced by the interaction of inhibitory intermediate neurons and excitatory pyramidal cells in the brain network. Therefore, 纬-oscillations reflect the advanced functions of the brain and have been widely used in the study of the related mechanisms of learning and memory functions. Neurodegenerative diseases, such as Alzheimer's disease (Alzheimer's disease,AD) and psychotic diseases, such as schizophrenia, suffer from impaired gamma oscillations. Recent studies have found that light stimulation at 纬-frequency reduces the production of A 尾 in hippocampus of AD model rats. Intracellular signal molecules and kinases, such as AC/PKA,PI3/Akt (PKB), PKC and AMPK,HDAC, play an important role in synaptic transmission and synaptic plasticity. Our research aims to explore the regulatory effects of these intracellular signal molecules and kinases on 纬 oscillation in order to understand the regulatory factors of 纬 oscillation and to provide new research ideas and therapeutic targets for clinical diseases related to learning and memory impairment. Objective to investigate the effects of intracellular signal molecules and kinases on rat hippocampal 纬 oscillation and its regulatory mechanism. Methods 1Cellular field potential recording 纬-oscillations in male SD rats for 6 weeks were studied. After anesthesia with 10% chloral hydrate, the cerebrospinal fluid (CSF) at 0 鈩，
本文编号：2448790
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