急性和慢性低O2高CO2大鼠海马线粒体生物合成改变及其与认知障碍的关系

Abstract
Figure/Table
References (0)
Related Citation (15)

Download: PDF (1661 KB) HTML (1 KB)
Export: BibTeX | EndNote (RIS)

Abstract Objective: To investigate the relationship between changes of mitochondrial biogenesis and learning and memory impairment in rats after acute or chronic exposure to hypoxia-hypercapnia. Methods: Forty eight SD male rats were randomly divided into three groups by the random number tables method as follows: the normal control group, the acute hypoxia-hypercapnia group, the chronic hypoxia-hypercapnia group. The cognitive ability was assessed by the Morris water maze. The mitochondrial structure was observed by the electron-microscopy. The protein expression of PGC-1α, NRF-1, TFAM were measured by the western blot. The copy number of mtDNA was detected by Real-Time PCR. Results: After exposure, the acute group performed almost similar to the normal control group in exploring the hidden platform. While the chronic group displayed worse performance during navigation test (P<0.05). In the probe trial on the last day, the acute group showed no difference with the normal control group, the crossing number of the chronic group was decreased (P<0.05). The electron-microscopy showed the mitochondrial structure of the acute group showed no obvious damage. The mitochondrial membrane of the chronic group was edema and obscure, partially destroyed, and the cristae was loosen and disorganized, partially disappeared. Western blot showed the protein expression of PGC-1α (P<0.01), NRF-1 (P<0.05), TFAM (P<0.05) were significantly increased in the acute group, but all markedly decreased in the chronic group. Real time PCR showed acute exposure induced an increase of the mtDNA copy number (P<0.01), while the expression in the chronic group significantly down-regulated (P<0.05). Conclusion: The downregulation of mitochondrial biogenesis may contribute to the cognitive function defects of long-term hypoxia-hypercapnia exposure rats.

Key words： hypoxia hypercapnia mitochondria cognitive mtDNA rats

Received: 10 June 2018

	Service
	E-mail this article
	Add to my bookshelf
	Add to citation manager
	E-mail Alert
	RSS
	Articles by authors
	MIN Jingjing
	GU Qun
	CHEN Qi
	WANG Xiaotong.

URL:

https://xb.wmu.edu.cn/EN/ OR https://xb.wmu.edu.cn/EN/Y2018/V48/I12/871

[1] PARK S K. Trajectories of change in cognitive function in people with COPD[J]. J Clin Nurs, 2018, 27(7-8): 1529-1542.
[2] OUELLETTE D R, LAVOIE K L. Recognition, diagnosis, and treatment of cognitive and psychiatric disorders in patients with COPD[J]. Int J Chron Obstruct Pulmon Dis, 2017, 12: 639-650.
[3] 吴彬, 金露, 王小同, 等. 慢性低氧高二氧化碳对小鼠大脑线粒体功能的影响[J]. 温州医学院学报, 2010, 40(2): 115-118.
[4] 邵胜敏, 陈松芳, 李勇, 等. 慢性低O2高CO2对大鼠海马 Bcl-2, Bax基因表达和细胞凋亡的影响[J]. 温州医学院学报, 2008, 38(1): 1-3.
[5] 李勇, 邓小龙, 邵胜敏, 等. c-Jun氨基末端激酶在慢性低O2高CO2大鼠海马损伤中的作用[J]. 中国病理生理杂志, 2009, 25(5): 914-918.
[6] 林盈盈, 陈轲扬, 霍鑫龙, 等. 慢性低氧高二氧化碳大鼠记忆障碍与脑内胆碱能失调的关系[J]. 中华神经科杂志, 2013, 46(1): 47-50.
[7] IYER S, KHAN S, PORTELL F, et al. 5.Protein-mediated mtDNA transfection (“Protofection®”) increases respiration and mitochondrial DNA gene copy numbers and expression in G11778A LHON cybrids[J]. Mitochondrion, 2009, 9(1): 62.
[8] PICCA A, LEZZA A M. Regulation of mitochondrial biogenesis through TFAM-mitochondrial DNA interactions: useful insights from aging and calorie restriction studies[J]. Mitochondrion, 2015, 25: 67-75.
[9] ST-PIERRE J, DRORI S, ULDRY M, et al. Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators[J]. Cell, 2006, 127(2): 397-408.
[10] BERTONI-FREDDARI C, FATTORETTI P, CASOLI T, et al. Neuronal apoptosis in Alzheimer’s disease:the role of age-related mitochondrial metabolic [J]. Ann N Y Acad Sci, 2009, 1171(1): 18-24.
[11] IYER S, THOMAS R R, PORTELL F R, et al. Recombinant mitochondrial transcription factor A with N-terminal mitochondrial transduction domain increases respiration and mitochondrial gene expression[J]. Mitochondrion, 2009, 9(3): 196-203.
[12] YAO K, ZHANG W W, YAO L, et al. Carvedilol promotes mitochondrial biogenesis by regulating the PGC-1/TFAM pathway in human umbilical vein endothelial cells (HUVECs)[J]. Biochem Biophys Res Commun, 2016, 470(4): 961-966.
[13] DOMINY J E, PUIGSERVER P. Mitochondrial biogenesis through activation of nuclear signaling proteins[J]. Cold Spring Harb Perspect Biol, 2013, 5(7).pii: a015008.
[14] VISCOMI C, BOTTANI E, CIVILETTO G, et al. In vivo correction of COX deficiency by activation of the AMPK/PGC-1α axis[J]. Cell Metab, 2011, 14(1): 80-90.
[15] SRIVASTAVA S, DIAZ F, IOMMARINI L, et al. PGC-1α/β induced expression partially compensates for respiratory chain defects in cells from patients with mitochondrial disorders[J]. Hum Mol Genet, 2009, 18(10): 1805-1812.
[16] VERMA M, WILLS Z P, CHU C T. Excitatory dendritic mitochondrial calcium toxicity: Implications for Parkinson’s and other neurodegenerative diseases[J]. Front Neurosci, 2018, 12: 523.
[17] NISSANKA N, MORAES C T. Mitochondrial DNA damage and reactive oxygen species in neurodegenerative disease[J]. FEBS Lett, 2018, 592(5): 728-742.
[18] CHEN H, HU C J, HE Y Y, et al. Reduction and restoration of mitochondrial DNA content after focal cerebral ischemia/reperfusion[J]. Stroke, 2001, 32(10): 2382-2387.
[19] LIANG H L, WONG-RILEY M T. Activity-dependent regulation of nuclear respiratory factor-1, nuclear respiratory factor-2, and peroxisome proliferator-activated receptor gamma coactivator-1 in neurons[J]. Neuroreport, 2006, 17(4): 401-405.
[20] ZHU P, HU S, JIN Q, et al. Ripk3 promotes ER stress-induced necroptosis in cardiac IR injury: a mechanism involving calcium overload/XO/ROS/mPTP pathway[J]. Redox Biol, 2018, 16: 157-168.
[21] MIN J, HUO X, QIN Y, et al. Protective effect of Dl-3n-butylphthalide on learning and memory impairment induced by chronic intermittent hypoxia-hypercapnia exposure[J]. Sci Rep, 2014, 4: 5555.