Abnormal expression of AMPA receptor in hippocampus of senescence accelerated mouse prone 8 correlated to synaptic plasticity

doi:10.3969/j.issn.0529-1356.2014.01.003

Abstract

Abstract:

Objective To observe the expression differences of AMPA receptor in hippocampal neurons between SAMP8 and SAMR1 and to explore the pathogenesis of Alzheimer’S disease(AD). Methods Male SAMP8 mice of 10-month old were taken as animal model of AD and SAMR1 mice were taken as control group. Morris water maze(MWM), electron microscope and western blotting were used in this study. Results Comparing with the control group, the model group had significant learning impairment and memory retention deficits. The thickness of post synaptic density(PSD) and the curvature of the synaptic interface in the model group dicrease. The width of synaptic cleft in the model group increased. The expression of GluR2 in the model group dicreased. There were no significant differences in the expression of GluR1 between two groups. Conclusions Impaired synaptic plasticity mediated by pathological alteration of AMPA receptor in hippocampus mey be the pathogenesis underlying learning and memory disorders of AD.

Key words: Senescence accelerated mouse prone 8, Alzheimer’s disease, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor, Synaptic plasticity, Learning , and memory, Morris water maze, Western blotting, Mouse

FENG Min ZHANG Ying-jun LU Juan XIONG Yin-yi WU Qiao-feng YU Mei-ling LU Sheng-feng YU Shu-guang*. Abnormal expression of AMPA receptor in hippocampus of senescence accelerated mouse prone 8 correlated to synaptic plasticity[J]. AAS, 2014, 45(1): 15-19.

References

［1］Newpher TM, Ehlers MD. Glutamate receptor dynamics in dendritic microdomains［J］. Neuron,2008,58(4):472-497.
［2］Helmut WK,Roberto M. Synaptic AMPA receptor plasticity and behavior［J］. Neuron, 2009,61(3):340-350.
［3］Ikonomovic MD, Mizukami K, Davies P, et al.The loss of GluR2(3) immunoreactivity precedes neurofibrillary tangle formation in the entorhinal cortex and hippocampus of Alzheimer brains［J］. J Neuropathol Exp Neurol,1997,56(9):1018-1027.
［4］Zhao WQ, Santini F, Breese R，et al. Inhibition of calcineurin-mediated endocytosis and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors prevents amyloid beta oligomer-induced synaptic disruption［J］.J Biol Chem,2010,285(10):7619-7632.
［5］Morley JE, Farr SA, Kumar VB, et al. The SAMP8 mouse: a nodel to develop therapeutic interventions for Alzheimer’s disease［J］.Curr Pharm Des,2012,18(8):1123-1130.
［6］Vorhees CV, Williams MT. Morris water maze: procedures for assessing spatial and related forms of learning and memory［J］.Nat Protoc,2006,1(2):848-858.
［7］Jones DG, Calverley RK. Frequency of occurrence of perforated synapses in developing rat neocortex ［J］.Neurosci Lett,1991, 129( 2):189-192.
［8］Jones DG, Devon RM. An uhrastructural study into the effect of pentobarbition on synaptic organization［J］.Brain Res,1978,147(1):47-63.
［9］Takeda T, Hosokawa M, Higuchi K. Senescence-accelerated mouse (SAM): a novel murine model of senescence［J］. Exp Gerontol, 1997,32(12):105-109.
［10］Takahashi R. Anti-aging studies on the senescence accelerated mouse (SAM) strains ［J］. Yakugaku Zasshi，2010,130(1):11-18.( in Japanese)
［11］Pallas M, Camins A, Smith MA, et al. From aging to Alzheimer’s disease: unveiling “the switch” with the senescence-accelerated mouse model (SAMP8) ［J］.J Alzheimers Dis, 2008,15(4):615-624.
［12］Cui HX，Li Sh，Gu P，et al. Effects of androgen on learning and memory ability and hippocampus neurons in SAMP8 mouse ［J］. Acta Anatomica Sinica, 2008,39(3):365-369.(in Chinese)
崔慧先;李莎;顾平,等.雄激素对SAMP8小鼠学习记忆能力及海马神经元的影响［J］.解剖学报, 2008,39(3):365-369. 
［13］Cui HX, Xie GSh, Li Sh, et al. Effects of dihydrotestosterone on synaptic plasticity and the expression of N-methyl-D-aspartate receptor 1 in CA1 region of hippocampus in SAMP8 mouse ［J］. Acta Anatomica Sinica, 2010,41(6):809-813. (in Chinese)
崔慧先,解国圣,李莎,等.双氢睾酮对快速老化小鼠海马CAl区突触可塑性和N-甲基-D-天冬氨酸受体1的影响［J］. 解剖学报,2010,41(6):809-813.
［14］Isaac JT, Ashby MC, McBain CJ. The role of the GluR2 subunit in AMPA receptor function and synaptic plasticity［J］. Neuron,2007,54(6):859-871.
［15］Savtchouk I, Liu SJ. Remodeling of synaptic AMPA receptor subtype alters the probability and pattern of action potential firing［J］. J Neurosci, 2011,31(2): 501-511.
［16］Parameshwaran K, Dhanasekaran M, Suppiramaniam V. Amyloid beta peptides and glutamatergic synaptic dysregulation［J］. Exp Neurol, 2008, 210(1): 7-13.
［17］Liang Z, Liu F, Iqbal K, et al. Dysregulation of tau phosphoryla-tion in mouse brain during excitotoxic damage［J］. J Alzheimers Dis, 2009, 17(3):531-539.
［18］Small SA, Perera GM, DeLaPaz R, et al. Differential regional dysfunction of the hippocampal formation amongelderly with memory decline and Alzheimer’s disease［J］. Ann Neurol,1999, 45(4):466-472.
［19］Craig AM, Blackstone CD, Huganir RL, et al. The distribution of glutamate receptors in cultured rat hippocampal neurons: postsynaptic clustering of AMPA-selective subunits［J］. Neuron,1993,10(6):1055-1068.
［20］Jayakar SS, Dikshit M.AMPA receptor regulation mechanisms: future target for safer neuroprotective drugs［J］.Int J Neurosci,2004,114(6):695-734.

[1]	HONG Xiao-min LI San-qiang CUI Qin-yi ZHENG Run-yue YANG Meng-li LUO Ren-li LI Qian-hui. Nuclear factor-κB signaling pathway and gender differences in alcoholic liver fibrosis [J]. Acta Anatomica Sinica, 2024, 55(1): 55-61.
[2]	WEI Xi-xi LI Chao-hong ZHAO Chen-lu TANG Jia-ping LIU Yu-zhen. Characterization of group Ⅰ metabotropic glutamate receptors in rat superior cervical ganglion and their changes following chronic intermittent hypoxia [J]. Acta Anatomica Sinica, 2024, 55(1): 3-9.
[3]	YUAN Lei YANG Zhi-wei YANG Hui LIU Zheng-hai HE Jie WAN Wei. Panax notoginseng saponin relieving the inflammatory pain caused by complete Freund’s adjuvant by inhibiting the activation of astrocytes in mice [J]. Acta Anatomica Sinica, 2024, 55(1): 25-31.
[4]	MA Ting-ting CHEN Jian-hong LIU Ai-cui LI Hai-ning. Role of inhibiting lncRNA TUG1 to down-regulate nucleotide binding oligomerization domain like receptor protein 1 inflammasome in delaying the progression of Alzheimer’s disease [J]. Acta Anatomica Sinica, 2024, 55(1): 32-42.
[5]	ZOU Cheng-gong FENG Hao CHEN Bing TANG Hui SHAO Chuan SUN Mou YANG Rong HE Jia-quan . Research on the dynamic changes of neurological dysfunction and cognitive function impairment in traumatic brain injury [J]. Acta Anatomica Sinica, 2024, 55(1): 43-48.
[6]	LÜ Hai-yan SHEN Xi-ya ZHAO Fu-sheng ZHU Mei . Effects of tricholoma matsutake polysaccharides on 1-methy-4-pehnyl-pyridine ion-induced PC12 cell damage [J]. Acta Anatomica Sinica, 2024, 55(1): 49-54.
[7]	ZHENG Li-ping LIU Xia DU Xiao-hua WU Ya-juan LIU Shan-shan . Expression and distribution of brain-derived neurotrophic factor in different cerebrum regions of yak and cattle [J]. Acta Anatomica Sinica, 2024, 55(1): 10-16.
[8]	HAO Yong-ming GUO Lei ZHOU Cheng-hui PEI Han-jun LI Li ZHAO Zhe . Establishment of a rat model of myocardial hypertrophy by a modified abdominal aortic coarctation method [J]. Acta Anatomica Sinica, 2024, 55(1): 120-124.
[9]	XU Ya-ping YU Yue-xin CHEN Jin-fu WANG Ke-ke GUO Zhikun . Structural distribution and mechanism of elastic fibers and collagen fibers in ventricular interstitium of aged rats [J]. Acta Anatomica Sinica, 2023, 54(6): 716-721.
[10]	WANG Wen-juan DING Yu-tong SU Hao REN Jie SUN Yan-rong WANG Han-fei LU Jia-li ZHANG Lin-qian BAI Yu QIN Li-hua. Changes of Nogo-A expression in hippocampus and striatum of rats under low estrogen condition [J]. Acta Anatomica Sinica, 2023, 54(6): 620-627.
[11]	ZHANG Qin YANG Jun-xia JIANG Qing-song. Effect of fosinopril on angiotensin converting enzyme 2 and vascular endothelial growth factor in diabetic retinopathy mice [J]. Acta Anatomica Sinica, 2023, 54(6): 628-634.
[12]	CHEN Zi-xuan SI Li-na SHU Wei-han ZHANG Xin WEI Chen-yang CHENG Lu-yang YANG Song-he QIAO Yue-bing. Mechanism of melatonin regulation of PI3K/Akt/mTOR signaling in hypothalamus delaying the initiation of puberty in female mice mice [J]. Acta Anatomica Sinica, 2023, 54(6): 644-651.
[13]	LIANG Pan-pan YU Ai-mei DU Jing KOU Wen-hui WANG Huan-huan SONG Ai-xia. Inhibitory effect of sodium ferulate on inflammatory response in migraine rats based on c-Jun N-terminal kinase/p38 mitogen-activated protein kinase signaling pathway [J]. Acta Anatomica Sinica, 2023, 54(6): 652-659.
[14]	XU Ying LIU Bin ZHENG Xing HE Zong-zhao. Role and mechanism of complement C3a receptor in the cognitive impairment of septic rats induced by cecal ligation and perforation [J]. Acta Anatomica Sinica, 2023, 54(6): 668-675.
[15]	LIU Zhe-chuan LI Kun MA Shuai-nan MENG Jia-qi WANG Yan-qin. Effects of liraglutide on inflammation and mitochondrial fusion/division in Parkinson’s disease model of mice induced by paraquat [J]. Acta Anatomica Sinica, 2023, 54(6): 676-681.