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Different correlation patterns between EEG and memory after GABA receptor adjustment in normal middle-aged mice and AD model mice
- Acta Scientiarum Naturalium Universitatis Sunyatseni Vol. 61, Issue 3, Pages: 11-20(2022)
- 作者机构：
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
- 作者简介：
- 基金信息：
DOI：10.13471/j.cnki.acta.snus.2021E010
CLC： Q424Published：25 May 2022，
Published Online：15 June 2021，
Received：09 March 2021，
Accepted：23 April 2021
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周正,李连娥,段梦思等.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[J].中山大学学报(自然科学版),2022,61(03):11-20.
ZHOU Zheng,LI Liane,DUAN Mengsi,et al.Different correlation patterns between EEG and memory after GABA receptor adjustment in normal middle-aged mice and AD model mice[J].Acta Scientiarum Naturalium Universitatis Sunyatseni,2022,61(03):11-20.
周正,李连娥,段梦思等.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[J].中山大学学报(自然科学版),2022,61(03):11-20. DOI： 10.13471/j.cnki.acta.snus.2021E010.
ZHOU Zheng,LI Liane,DUAN Mengsi,et al.Different correlation patterns between EEG and memory after GABA receptor adjustment in normal middle-aged mice and AD model mice[J].Acta Scientiarum Naturalium Universitatis Sunyatseni,2022,61(03):11-20. DOI： 10.13471/j.cnki.acta.snus.2021E010.
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GABA
A
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。
Abstract
Symptoms including brain atrophy
neuronal loss
neurotansmitter imbalance and cognitive 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 electroencephalograms (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 GABA
A
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 correlation 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
bicuculline 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）bicucullineGABAAmuscimol空间记忆
Keywords
aging accelerationAlzheimer′s disease (AD)bicucullineGABAAmuscimolspatial memory
references
LUO X G， DING J Q， CHEN S D. Microglia in the aging brain： Relevance to neurodegeneration［J］. Mol Neurodegener， 2010， 5： 12.
HAN X， ZHANG T， LIU H， et al. Astrocyte senescence and Alzheimer's disease： A review［J］. Front Aging Neurosci， 2020， 12： 148.
HAKIM M A， BEHRINGER E J. Alzheimer’s disease as a condition of accelerated aging of cerebrovascular endothelial function［J］. The FASEB Journal， 2020， 34（S1）： 1.
BOCCARDI V， PELINI L， ERCOLANI S， et al. From cellular senescence to Alzheimer's disease： The role of telomere shortening［J］. Ageing Res Rev， 2015， 22： 1-8.
MOSHER K I， WYSS-CORAY T. Microglial dysfunction in brain aging and Alzheimer's disease［J］. Biochemical Pharmacology， 2014， 88（4）： 594-604.
TOEPPER M. Dissociating normal aging from Alzheimer's disease： A view from cognitive neuroscience［J］. Journal of Alzheimer's Disease， 2017， 57（2）： 331-352.
SANDYK R. The accelerated aging hypothesis of Parkinson's disease is not supported by the pattern of circadian melatonin secretion［J］. The International Journal of Neuroscience， 1997， 90（3/4）： 271-275.
NELSON P T， HEAD E， SCHMITT F A， et al. Alzheimer's disease is not "brain aging"： Neuropathological， genetic， and epidemiological human studies［J］. Acta Neuropathol， 2011， 121（5）： 571-587.
ROZYCKA A， LIGUZ-LECZNAR M. The space where aging acts： Focus on the GABAergic synapse［J］. Aging Cell， 2017， 16（4）： 634-643.
SCHMOLESKY M T， WANG Y， PU M， et al. Degradation of stimulus selectivity of visual cortical cells in senescent rhesus monkeys［J］. Nature Neuroscience， 2000， 3（4）： 384-390.
LEON-ESPINOSA G， de FELIPE J， MUNOZ A. Effects of amyloid-beta plaque proximity on the axon initial segment of pyramidal cells［J］. Journal of Alzheimer's Disease， 2012， 29（4）： 841-852.
LEI M， XU H， LI Z， et al. Soluble Aβ oligomers impair hippocampal LTP by disrupting glutamatergic/GABAergic balance［J］. Neurobiology of Disease， 2016， 85： 111-121.
PALOP J J， MUCKE L. Network abnormalities and interneuron dysfunction in Alzheimer disease［J］. Nature Reviews Neuroscience， 2016， 17（12）： 777-792.
NAVA-MESA M O， JIMENEZ-DIAZ L， YAJEYA J， et al. GABAergic neurotransmission and new strategies of neuromodulation to compensate synaptic dysfunction in early stages of Alzheimer's disease［J］. Frontiers in Cellular Neuroscience， 2014， 8： 167.
FU Y， LI L， WANG Y， et al. Role of GABAA receptors in EEG activity and spatial recognition memory in aged APP and PS1 double transgenic mice［J］. Neurochem Int， 2019， 131： 104542.
HARRISON D. Life span as a biomarker［R］. The Jackson Laboratory， 2011.
NIMMRICH V， DRAGUHN A， AXMACHER N. Neuronal network oscillations in neurodegenerative diseases［J］. Neuromolecular Medicine， 2015， 17（3）： 270-284.
LIU T， BAI W， YI H， et al. Functional connectivity in a rat model of Alzheimer's disease during a working memory task［J］. Current Alzheimer Research， 2014， 11（10）： 981-991.
LEISER S C， DUNLOP J， BOWLBY M R， et al. Aligning strategies for using EEG as a surrogate biomarker： A review of preclinical and clinical research［J］. Biochemical Pharmacology， 2011， 81（12）： 1408-1421.
del PERCIO C, DRINKENBURG W, LOPEZ S, et al. Ongoing electroencephalographic activity associated with cortical arousal in transgenic PDAPP mice (hAPP V717F)［J］.Current Alzheimer Research, 2018, 15(3): 259-272.
HIDISOGLU E， KANTAR-GOK D， ER H， et al. Alterations in spontaneous delta and gamma activity might provide clues to detect changes induced by amyloid-beta administration［J］.The European Journal of Neuroscience， 2018， 47（8）： 1013-1023.
PLATT B， DREVER B， KOSS D， et al. Abnormal cognition， sleep， EEG and brain metabolism in a novel knock-in Alzheimer mouse， PLB1［J］. PLoS One， 2011， 6（11）： e27068.
JYOTI A, PLANO A, RIEDEL G, et al. EEG, activity, and sleep architecture in a transgenic AbetaPPswe/PSEN1A246E Alzheimer's disease mouse［J］.Journal of Alzheimer's Disease, 2010, 22(3): 873-887.
ABD HAMID A I, GALL C, SPECK O, et al. Effects of alternating current stimulation on the healthy and diseased brain［J］.Frontiers in Neuroscience, 2015, 9: 391.
MARTORELL A J， PAULSON A L， SUK H J， et al. Multi-sensory gamma stimulation ameliorates Alzheimer's-associated pathology and improves cognition［J］. Cell， 2019， 177（2）： 256-271.
KLESCHEVNIKOV A M， BELICHENKO P V， VILLAR A J， et al. Hippocampal long-term potentiation suppressed by increased inhibition in the Ts65Dn mouse， a genetic model of Down syndrome［J］. J Neurosci， 2004， 24（37）： 8153-8160.
LI Y， SUN H， CHEN Z， et al. Implications of GABAergic neurotransmission in Alzheimer's disease［J］. Front Aging Neurosci， 2016， 8： 31.
MATSUYAMA S， TANIGUCHI T， KADOYAMA K， et al. Long-term potentiation-like facilitation through GABAA receptor blockade in the mouse dentate gyrus in vivo［J］. Neuroreport， 2008， 19（18）： 1809-1813.
PALOP J J， CHIN J， ROBERSON E D， et al. Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease［J］. Neuron， 2007， 55（5）： 697-711.
McQUAIL J A， FRAZIER C J， BIZON J L. Molecular aspects of age-related cognitive decline： The role of GABA signaling［J］. Trends in Molecular Medicine， 2015， 21（7）： 450-460.
JOHNSTON G A. Muscimol as an ionotropic GABA receptor agonist［J］. Neurochem Res, 2014, 39(10): 1942-1947.
GIBBS M E， JOHNSTON G A. Opposing roles for GABAA and GABAC receptors in short-term memory formation in young chicks［J］. Neuroscience， 2005， 131（3）： 567-576.
LEVENTHAL A G， WANG Y， PU M， et al. GABA and its agonists improved visual cortical function in senescent monkeys［J］. Science， 2003， 300（5620）： 812-815.
PALPAGAMA T H， SAGNIEZ M， KIM S， et al. GABA（A） receptors are well preserved in the hippocampus of aged mice［J］. eNeuro， 2019， 6（4）：18.
RISSMAN R A, de BLAS A L, ARMSTRONG D M. GABA(A) receptors in aging and Alzheimer's disease［J］. Journal of Neurochemistry, 2007, 103(4):1285-1292.
LIMON A， REYES-RUIZ J M， MILEDI R. Loss of functional GABA（A） receptors in the Alzheimer diseased brain ［J］. Proceedings of the National Academy of Sciences of the United States of America， 2012， 109（25）： 10071-10076.
KOELEWIJN L， BOMPAS A， TALES A， et al. Alzheimer's disease disrupts alpha and beta-band resting-state oscillatory network connectivity［J］. Clin Neurophysiol， 2017， 128（11）： 2347-2357.
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