[1]王方,黄朝云,徐敏.不同鼠龄在慢性间断性缺氧相关认知损害中的作用及机制探讨[J].卒中与神经疾病杂志,2017,24(03):208-213.[doi:10.3969/j.issn.1007-0478.2017.03.010]
 Wang Fang,Huang Chaoyun,Xu Min..The role of aging related cognitive impairment and mechanism in chronic intermittent hypoxia[J].Stroke and Nervous Diseases,2017,24(03):208-213.[doi:10.3969/j.issn.1007-0478.2017.03.010]
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不同鼠龄在慢性间断性缺氧相关认知损害中的作用及机制探讨()
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《卒中与神经疾病》杂志[ISSN:1007-0478/CN:42-1402/R]

卷:
第24卷
期数:
2017年03期
页码:
208-213
栏目:
论 著
出版日期:
2017-06-26

文章信息/Info

Title:
The role of aging related cognitive impairment and mechanism in chronic intermittent hypoxia
文章编号:
1007-0478(2017)03-0208-06
作者:
王方黄朝云徐敏
430071 武汉大学中南医院神经内科[王方 黄朝云
Author(s):
Wang Fang Huang Chaoyun Xu Min.
Department of Neurdogy, Zhongnan Hospital, Wuhan University, Wuhan 430071
关键词:
老年 间断性缺氧 认知损害 胰岛素信号转导通路
Keywords:
Ageing Chronic intermittent hypoxia Cognitive impairment Insulin signaling pathway
分类号:
R742
DOI:
10.3969/j.issn.1007-0478.2017.03.010
摘要:
目的 阐明不同鼠龄在慢性间断性缺氧相关认知损害中的作用及可能机制。方法 采用改良的IH鼠箱建立慢性IH小鼠模型,利用Morris水迷宫检测青年和老年IH小鼠的认知功能; 通过氧疗的干预对比青年与老年小鼠认知损害及突触可塑性的改善程度,TUNEL法检测小鼠海马CA1区神经元凋亡情况,Western Blotting检测神经突触素、胰岛素信号通路蛋白[蛋白激酶B(Akt)、糖原合成激酶3β(GSK-3β)]的磷酸化表达水平变化。结果 老年小鼠IH组的逃避潜伏期最长,其海马CA1区见明显增多的TUNEL染色阳性细胞,脑细胞凋亡率最高(P<0.01),p-Akt、p-GSK3β表达水平显著降低(P<0.01),目标象限LD滞留时间与p-Akt、p-GSK3β均存在正相关。结论 老年使慢性间断性缺氧C57BL/6小鼠认知损害的易感性增加,可能的机制之一是调节胰岛素信号通路相关蛋白的表达异常。
Abstract:
ObjectiveTo explore the role of aging related cognitive impairment and the possible mechanism in chronic intermittent hypoxia.Methods A improved mice cage was used to set up the chronic intermittent hypoxia mice model,then the Morris water maze tested cognitive function of young and aged mice during chronic intermittent hypoxia.By oxygen therapy intervention,the degree of improvement of cognitive impairment and the synaptic plasticity was compared between young and aged mice.The apoptosis of neurons in mice hippocampus CA1 area was examined by TUNEL,and the expression level of synaptophysin, phosphorylated Akt(p-Akt)and phosphorylated GSK3β(p-GSK3β)proteins was examined by Western Blotting.Results In the aged group, the escape latency was significantly prolonged compared with the other groups, while the time of swimming in the platform quadrant significantly decreased(P<0.05), and the apoptosis rate of hippocampus neural increased(P<0.01),while the phosphorylated Akt(p-Akt)and phosphorylated GSK3β(p-GSK3β)proteins expression level was significantly reduced(P<0.01).There was a linear relationship between the p-Akt expression and time in target quadrant LD,as well as a linear relationship between the the p-GSK3β and time in target quadrant LD.Conclusion It was proposed that the aged could lead to susceptibility to intermittent hypoxia-induced cognitive impairment,and a possible mechanism was the regulating insulin signaling pathway related proteins expression.

参考文献/References:

[1] Lal C,Strange C,Bachman D.Neurocognitive impairment in obstructive sleep apnea[J].Chest,2012,141(6):1601-1610.
[2] Kawada T,Katsumata M,Inagaki H,et al.Sleep-disordered breathing and disorders of glucose metabolism[J].Diabetes Metab Syndr,2016,PMID:27612395,DOI:10.1016/j.dsx.2016.09.001
[3] Ng SS,Chan TO,To KW,et al.Prevalence of obstructive sleep apnea syndrome and CPAP adherence in the elderly Chinese population[J].PLoS One,2015,10(3):e0119829.
[4] Netzer NC,Ancoli-Israel S,Bliwise DL,et al.Principles of practice parameters for the treatment of sleep disordered breathing in the elderly and frail elderly: the consensus of the International Geriatric Sleep Medicine Task Force[J].Eur Respir J,2016,48(4):992-1018.
[5] Mattson MP.Energy intake and exercise as determinants of brain health and vulnerability to injury and disease[J].Cell Metab,2012,16(6):706-722.
[6] Rönnemaa E,Zethelius B,Sundel f J,et al.Glucose metabolism and the risk of Alzheimer's disease and dementia: a population-based 12 year follow-up study in 71-year-old men[J].Diabetologia,2009,52(8):1504-1510.
[7] Fagan KA.Selected contribution: pulmonary hypertension in mice following intermittent hypoxia[J].J Appl Physiol(1985),2001,90(6):2502-2507.
[8] 王璋,司良毅,廖友斌.大鼠睡眠呼吸暂停综合征动物模型的建立[J].中国实验动物学报,2006,14(1):40-43, 插5.
[9] Bromley-Brits K,Deng Y,Song W.Morris water maze test for learning and memory deficits in Alzheimer's disease model mice[J].J Vis Exp,2011(53).PMID:21808223,DOI:10.3791/2920
[10] Guidotti Breting LM,Tuminello ER,Duke Han S.Functional neuroimaging studies in normal aging[J].Curr Top Behav Neurosci,2012,10:91-111.
[11] Vernooij MW,Smits M.Structural neuroimaging in aging and alzheimer's disease[J].Neuroimaging Clin N Am,2012,22(1):33.
[12] Smith GS.Aging and neuroplasticity[J].Dialogues Clin Neurosci,2013,15(1):3-5.
[13] Decarli C,Kawas C,Morrison JH,et al.Session II: mechanisms of age-related cognitive change and targets for intervention: neural circuits, networks, and plasticity[J].J Gerontol A Biol Sci Med Sci,2012,67(7):747-753.
[14] Zimmerman ME,Aloia MS.Sleep-disordered breathing and cognition in older adults[J].Curr Neurol Neurosci Rep,2012,12(5):537-546.
[15] Cherniack EP,Cherniack NS.Obstructive sleep apnea, metabolic syndrome, and age: will geriatricians be caught asleep on the job?[J].Aging Clin Exp Res,2010,22(1):1-7.
[16] Zhang C,Li Y,Wang YI. Effect of intermittent hypoxia of sleep apnea on embryonic rat cortical neurons in vitro [J]. Lin chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi,2015,29(9):845-848.
[17] Yin X,Zhang X,Lv C,et al.Protocatechuic acid ameliorates neurocognitive functions impairment induced by chronic intermittent hypoxia[J].Sci Rep,2015,5:14507.
[18] Goldbart AD,Row BW,Kheirandish-Gozal L,et al.High fat/refined carbohydrate diet enhances the susceptibility to spatial learning deficits in rats exposed to intermittent hypoxia[J].Brain Res,2006,1090(1):190-196.
[19] Steen E,Terry BM,Rivera EJ,et al.Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease-is this type 3 diabetes?[J].Journal of Alzheimers Disease,2005,7(1):63-80.
[20] Cai M,Wang H,Li JJ,et al.The signaling mechanisms of hippocampal endoplasmic reticulum stress affecting neuronal plasticity-related protein levels in high fat diet-induced obese rats and the regulation of aerobic exercise[J].Brain Behav Immun,2016,57:347-359.

更新日期/Last Update: 2017-06-20