淀粉樣β蛋白抑制大鼠海馬theta節(jié)律并致行為脫抑制和空間記憶損傷
本文選題:淀粉樣β蛋白 + 海馬theta節(jié)律; 參考:《生理學(xué)報(bào)》2014年02期
【摘要】:海馬神經(jīng)元網(wǎng)絡(luò)振蕩與哺乳動(dòng)物學(xué)習(xí)記憶、焦慮及行為抑制密切相關(guān)。阿爾茨海默病患者早期表現(xiàn)出的認(rèn)知功能減退及行為脫抑制,極可能與海馬內(nèi)沉積的淀粉樣β蛋白(amyloid β protein,Aβ)損傷了海馬神經(jīng)元網(wǎng)絡(luò)電活動(dòng)有關(guān),但海馬注射Aβ能否在傷害學(xué)習(xí)記憶功能的同時(shí)也引起行為脫抑制和改變神經(jīng)元同步化活動(dòng),仍缺乏足夠的動(dòng)物實(shí)驗(yàn)證據(jù)。本研究利用Morris水迷宮、高架十字迷宮和在體局部場(chǎng)電位記錄技術(shù),觀察了海馬注射Aβ1 42寡聚體對(duì)大鼠空間學(xué)習(xí)記憶和行為抑制活動(dòng)的影響,并分析了海馬theta節(jié)律的改變。結(jié)果表明,與對(duì)照組相比,海馬注射Aβ1 42寡聚體兩周后:(1)大鼠在高架十字迷宮中焦慮性減低,出現(xiàn)明顯的行為脫抑制現(xiàn)象,去開(kāi)臂次數(shù)和在開(kāi)臂停留時(shí)間均明顯增加;(2)大鼠空間學(xué)習(xí)、記憶嚴(yán)重受損,水迷宮定位航行實(shí)驗(yàn)中尋找水下平臺(tái)的潛伏期明顯延長(zhǎng),空間探索實(shí)驗(yàn)中在原平臺(tái)象限的游泳時(shí)間百分比明顯減小;(3)大鼠海馬CA1區(qū)theta節(jié)律壓抑,由夾尾刺激誘導(dǎo)的theta節(jié)律的功率峰值明顯減低,而theta節(jié)律功率峰值對(duì)應(yīng)的頻率值未發(fā)生改變。以上結(jié)果表明,海馬注射Aβ1 42寡聚體可同時(shí)引起大鼠行為脫抑制、空間記憶損傷和海馬theta節(jié)律壓抑。這提示,AD患者出現(xiàn)的學(xué)習(xí)記憶能力障礙和精神行為異常很可能與Aβ對(duì)海馬神經(jīng)元網(wǎng)絡(luò)theta節(jié)律活動(dòng)的壓抑以及由此引起的突觸可塑性下調(diào)有關(guān)。
[Abstract]:Hippocampal neuronal network oscillation is closely related to mammalian learning and memory, anxiety and behavioral inhibition. Early cognitive impairment and behavioral deinhibition in patients with Alzheimer's disease may be related to amyloid 尾 protein A 尾 (amyloid 尾 protein A 尾), which impairs the electrical activity of hippocampal neurons. However, there is still insufficient evidence of whether hippocampal injection of A 尾 can injure learning and memory function, but also induce behavioral deinhibition and change neuronal synchronization. In this study, Morris water maze, elevated cross maze and in vivo local field potential recording techniques were used to observe the effects of A 尾 1 Oligomer on spatial learning, memory and behavioral inhibition in rats, and to analyze the changes of theta rhythm in hippocampus. The results showed that compared with the control group, the anxiety in the elevated cross labyrinth was decreased in rats injected with A 尾 1 42 oligomer in hippocampus two weeks later. The number of arm removal and the time of staying in the open arm increased significantly (P < 0.05). The spatial learning and memory of rats were severely damaged, and the latency of finding underwater platform in the water maze navigation experiment was prolonged obviously. In the space exploration experiment, the percentage of swimming time in the original platform quadrant was significantly reduced. (3) the theta rhythm in the CA1 region of the hippocampus was suppressed, and the peak power of the theta rhythm induced by the clip tail stimulation was significantly decreased. However, the frequency corresponding to the peak of theta rhythmic power did not change. These results suggest that the injection of A 尾 1 / 42 oligomer into the hippocampus can simultaneously induce behavioral deinhibition, spatial memory impairment and inhibition of theta rhythm in the hippocampus of rats. These results suggest that the disorder of learning and memory and the abnormal mental behavior in AD patients may be related to the inhibition of theta rhythm of hippocampal neuron network by A 尾 and the downregulation of synaptic plasticity caused by A 尾.
【作者單位】: 山西醫(yī)科大學(xué)生理學(xué)系 細(xì)胞生理學(xué)省部共建教育部重點(diǎn)實(shí)驗(yàn)室;山西醫(yī)科大學(xué)基礎(chǔ)醫(yī)學(xué)院機(jī)能實(shí)驗(yàn)中心;
【基金】:supported by the National Natural Science Foundation of China(No.31271201) the Special Foundation for the Doctoral Program of Higher Education of Ministry of Education,China(No.20101417110001) the Natural Science Foundation of Shanxi Province,China(No.2010011049-3,2010-51)
【分類號(hào)】:R749.16
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