【摘要】：背景γ振蕩是神經網絡功能的一個特征,存在于多個腦區(qū),主要由腦網絡中的抑制性中間神經元及興奮性錐體細胞相互作用產生,在注意力高度集中、探索行為及學習記憶活動中明顯增強,因此,γ振蕩反映了腦的高級功能,并被廣泛應用于學習和記憶功能相關機制的研究。而神經退行性疾病,如阿爾茨海默病(Alzheimer’s disease,AD)及精神類疾病,如精神分裂癥患者的γ振蕩受損。最近的研究發(fā)現(xiàn)γ頻率的光刺激減少了AD模型鼠海馬Aβ的產生。細胞內信號分子及激酶,如AC/PKA、PI3/Akt(PKB)、PKC及AMPK、HDAC等在突觸傳遞及突觸可塑性中起重要作用,但其是否參與調節(jié)γ振蕩并不清楚。我們的研究旨在探討這些細胞內信號分子及激酶對γ振蕩的調控作用,以了解γ振蕩的可調控因素及對學習記憶功能受損相關的臨床疾病提供新的科研思路和治療靶點。目的探討細胞內信號分子及激酶對大鼠海馬γ振蕩的影響及調控機制。方法1細胞外場電位記錄γ振蕩實驗對象為4~6周的雄性SD大鼠,用10%水合氯醛麻醉成功后,抽取0℃的切片腦脊液經左心室系統(tǒng)灌流至四肢變白后,快速斷頭取腦并固定,用振動切片機將腦組織水平切成350μm厚的腦片。然后將含有海馬結構的腦片迅速轉移到孵育槽上孵育60分鐘后,用紅藻氨酸受體激動劑(Kainate,KA)可誘導出穩(wěn)定持久的γ頻率振蕩。實驗采用細胞外微電極方式記錄電活動。2觀察細胞內信號分子及激酶抑制劑對γ振蕩功率譜及峰值頻率的影響。3統(tǒng)計分析用SPike 2軟件對數(shù)據(jù)進行離線分析,實驗數(shù)據(jù)使用Sigmastat軟件統(tǒng)計。實驗結果以平均值±標準差來表示。如果P0.05,則被認為其具有統(tǒng)計學意義。結果1 AC抑制劑MDLL-12330A(MDL),PKA抑制劑H89,ERK抑制劑U0126及PKC抑制劑G6983對海馬KA誘導的γ振蕩無明顯影響。2 PI3K抑制劑wortmannin對γ振蕩無明顯作用,而Akt抑制劑TCBN增加了海馬γ振蕩的能譜(P0.05)。3 AMPK抑制劑CC增加了海馬γ振蕩的能譜(P0.01)。4非特異性HDAC抑制劑SAHA增加了KA誘導的γ振蕩的能譜(P0.001),選擇性HDAC抑制劑PD106和HDAC6抑制劑NXT也增加了γ振蕩的能譜(P0.05)。結論海馬KA誘導的γ振蕩存在Akt、HDAC、AMPK的激活,而這種激活對γ振蕩存在負性調節(jié)作用,這種負性調節(jié)作用提示γ振蕩存在自穩(wěn)態(tài)調節(jié)機制。AC、PKA、ERK、PI3K、PKC不參與海馬KA誘導的γ振蕩。
[Abstract]:Background 緯 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, 緯-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 緯-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 緯 oscillation in order to understand the regulatory factors of 緯 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 緯 oscillation and its regulatory mechanism. Methods 1Cellular field potential recording 緯-oscillations in male SD rats for 6 weeks were studied. After anesthesia with 10% chloral hydrate, the cerebrospinal fluid (CSF) at 0 鈩，

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