健康成年小鼠和AD模型小鼠在GABA受体调节后脑电与记忆的不同相关模式  

Different correlation patterns between EEG and memory after GABA receptor adjustment in normal middle-aged mice and AD model mice

作　　者：周正 李连娥 段梦思 孙华英 易虎 付玉 ZHOU Zheng;LI Liane;DUAN Mengsi;SUN Huaying;YI Hu;FU Yu(Medical School,Kunming University of Science&Technology,Kunming 650500,China;CollegeofBiologyandFoodEngineering,ChongqingThreeGorgesUniversity,Chongqing 404100,China;School of Chinese Materia Medica,Yunnan University of Chinese Medicine,Kunming 650500,China;School of Information Science and Engineering,Yunnan University,Kunming 650091,China)

机构地区：[1]昆明理工大学医学院,云南昆明650500 [2]重庆三峡学院生物与食品工程学院,重庆404100 [3]云南中医药大学中药学院,云南昆明650500 [4]云南大学信息科学与工程学院,云南昆明650091

出　　处：《中山大学学报（自然科学版）（中英文）》2022年第3期11-20,共10页Acta Scientiarum Naturalium Universitatis Sunyatseni

基　　金：国家自然科学基金(81760258,81560221,81703497,61972158);云南省自然科学基金(2017FB125,2017FD067)。

摘　　要：正常衰老和阿尔茨海默病(AD,Alzheimer′s disease)都与大脑萎缩、神经元丢失、神经递质紊乱以及认知退化有关,并且这些变化在AD中更为明显,进展更加快速。因此,有人提出了AD表现出加速衰老的这一假设。AD和正常衰老都涉及兴奋/抑制(E/I)神经传递的失衡,尤其是在γ-氨基丁酸(GABA)抑制功能障碍中。在本研究中,我们在腹腔注射muscimol和bicuculline调节GABAA的E/I平衡后,记录了成年(~12个月)WT小鼠和AD小鼠(APP/PS1)在Y-迷宫期间海马和前额叶皮层的脑电(EEG),并对小鼠的EEG与记忆之间进行了偏相关分析。总体而言,WT和AD小鼠在EEG活动和行为记忆表现之间显示出不同的相关模式。WT小鼠在较宽的频带范围内(2~100 Hz,4~8 Hz除外)观察到脑电活动的显著相关性,在AD小鼠中则主要发生在低频带(delta-theta,2~8 Hz)。此外,muscimol和bicuculline都有助于改善AD小鼠的记忆能力,但bicuculline降低了WT小鼠的记忆能力。因此,我们的数据表明AD病理与正常衰老过程截然不同,提示AD可能不是加速衰老的必然结果。这项研究通过调节E/I平衡来影响低频EEG活动,有助于认知康复,从而揭示了对未来AD治疗的新见解。Symptoms including brain atrophy,neuronal loss,neurotansmitter imbalance and cogni‐tive decline are generally associated with Alzheimer's disease(AD),also occur in normal aging.Thus,comparing the differences between normal aging and AD is of interest to test the accelerated aging hypothesis of AD.An imbalance between excitatory/inhibitory(E/I)neurotransmission especially that originated from the dysfunction in gamma-aminobutyric acid(GABA)inhibition is involved in both AD and normal aging.In the present study,we performed correlation analyses between electroencepha‐lograms(EEGs)and memory in middle-aged(~12 months old)wild-type mice(WT)and AD model mice(APP/PS1)after E/I balance adjustment via GABAA agonist muscimol and antagonist bicuculline administration(0.1 mg/kg intraperitoneally).Specifically,EEGs of the hippocampus and prefrontal cortex were recorded during Y-maze performance.Overall,WT and AD mice showed different correla‐tion patterns between EEG activity and behavioral memory performance.Significant correlations were observed in EEG activity across a wider range of frequency bands(2-100 Hz,except 4-8 Hz)in WT mice,but were mainly observed in low frequency bands(delta-theta,2-8 Hz)in AD mice.In addition,muscimol and bicuculline treatment contributed to better brain function in AD mice;in contrast,bicu‐culline administration resulted in poorer brain function in WT mice.Thus,our study indicates that AD pathology is distinct from the normal aging process,and the data may not support the accelerated aging hypothesis of AD.Importantly,this work reveals new insights into future AD treatment by influencing low-frequency EEG activity through E/I balance adjustment,thereby aiding cognitive recovery.

关 键 词：衰老加速 阿尔茨海默病(Alzheimer′s disease AD) BICUCULLINE GABA_(A) MUSCIMOL 空间记忆 

分 类 号：Q424[生物学—神经生物学]