1890 Altaman. 15~20kd DNA. b(cytb) ATP 2 7 (ND1,2,3,4,4L,5 6) [1,2] ) NADH. 37 mtdna. Ca 2+ B Advances in Psychological Science

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1 Advances in Psychological Science * Ca 2+ Ca 2+ B Altaman Ca 2+ 15~20kd DNA 22 trnas 2 rrnas b(cytb) ATP 2 1 c(cytc) 3 (COX ) NADH 7 (ND1,2,3,4,4L,5 6) [1,2] * [2001]39 xigengsi@snnu.edu.cn mtdna [3] 341

2 Ca ( - ) NADH-Q -Q ATP 2.1 CO 2 NADH FADH 2 H + H + O 2 H 2 O H + ATP ADP Pi ATP ATP 95 ATP Bertoni-Freddari ATP Ca 2+ < ~26 [6] (uniporter) 2Na + /Ca 2+ 2Na + /Ca 2+ exchanger NCE mitochondrial permeablize [7] transition pore MPTP Ca 2+ [4,5]

3 Ca 2+ Ca 2+ Ca 2+ [Ca 2+ ] Ca 2+ [8] Na + Na + Na + -Ca 2+ 1/6 Ca 2+ Na + -Ca hydroxy-2 -nonenal HNE Ca 2+ [Ca 2+ ] [9] Ca 2+ + AD AD [12] (PDHC) Ca 2+ (KGDHC) (COX) [13] (positron emission tomography PET) AD Ca 2+ [10,11] Na + Ca 2+ Ca Ca 2+ Y- Long-term potentiation LTP LTP LTP - Ca 2+ Ca 2+ Ca 2+ LTP [Ca 2+ ] LTP

4 [14,15] LTP Ca 2+ PKC CaMKII Ca 2+ Ca 2+ LTP m C(Cytc) (AIF) C 2.3 C 50 C C C ATP/dATP Apaf1(apoptoticprotease activating factors) (apopto some) [20~22] Apaf 1 procaspase 9 Caspase 3 caspases Bcl2 - C [24] Bcl2 [16~18] 2.4 [19] [25] [23] Huntingtin

5 congenic quartet proof-reading DNA DNA DNA 3 5 [26] 25 DNA [29] DNA -L- DNA Acetyl-L-Carnitine α- DNA 10 DNA [30] PolgA DNA [27] 3 mtdna 483bp % 3 mtdna mtdna [28] mtdna mtdna mtdna DNA knock in DNA mtdna polymerase

6 Neural Transmission, 1998, 105: 855~870 Morphological plasticity of synaptic mitochondria during aging. Brain Research, 1993, 628: 193~200 [7],,.., Mar. 2000, 16(1): 40~44 [8] Wagner O I, Lifshitz J, Janmey P A, et al. Mechanisms of Mitochondria-Neurofilament Interactions. The Journal of Neuroscience, October 8, 2003, 23(27): 9046~9058 [9] Floyd R A, Hensley K. Oxidative stress in brain aging. Implications for therapeutics of neurodegenerative diseases. Neurobiology of Aging, 2002 Sep-Oct, 23(5): 795~807 [10] Rapoport S I, Hatanpaa K, Brady D R, et al. Brain energy metabolism, cognitive function and down-regulated oxidative phosphorylation in Alzheimer disease. Neurodegeneration, 1996 Dec, 5(4): 473~6 [11] Gibson E, Sheu K F, Blass J P. Abnormalities of mitochondrial enzymes in Alzheimer s disease. Journal of [12] Levy M, Faas G C, Saggau P, et al. Mitochondrial Regulation of Synaptic Plasticity in the Hippocampus. The Journal of Biological Chemistry, 2003 May 16, 278(20): 17727~34 [13] Toescu E C, Xiong J. Metabolic substrates of neuronal aging. Annals of the New York Academy of Sciences Jun, [1] Lee W J, Kocher T D. Complete sequence of a sea lampey (Pe tro myzon marinus) mitochondrial genome: early establishment of the vertebrate genome organization. Genetics, 1995, 139(2): 873~887 [2] Gares R. Drosophila melanogaster mitochondrial DNA: gene organization and evolutionary considerations. Genetics, 1998, 118(4): 649~663 [3] Turnbull D M, Lightolers R N. An essential guide to mtdna maintenace. Nature Genetics, 1998, 18: 199~200 [4] Duchen M R. Contributions of mitochondria to animal physiology: from homeostatic sensor to calcium signaling and cell death. The Journal of Physiology, 1999, 516(1): 1~17 [5] Richard J M. Mitochondria - the Kraken wakes. Trends Neuroscience, 1998, 21(3): 95~97 [6] Bertoni-Freddari C, Fattoretti P, Casoli T, et al. 1019: 19~23 [14] Yang S N, Tang Y G, Zucker R S. Selective induction of LTP and LDP by postsynaptic [Ca 2+ ] i elevation. The Journal of Neurophysiology, 1999, 81: 781~787 [15],.., 2001, 32(1): 35~38 [16] Liu X, Kin C N, Yang J, et al. Induction of apoptotic program in cell-free extracts: requirement for datp and cytochrome c. Cell, 1996, 86: 147~157 [17] Ellerby H M, Martin S J, Ellerby L M, et al. Establishment of a cell-free system of neuronal apoptosis: comparison of premitochondrial, mitochondrial, and post- mitochondrial phases. The Journal of Neuroscience, 1997, 17: 6165~6178 [18] David G, Samantha L. Mitochondria and Neuronal Survival. Physiological Reviews, 2000 January, 80: 315~360 [19] Panov A V, Gutekunst C A, Leavitt B R, et al. Early

7 mitochondrial calcium defects in Huntington's disease are a direct effect of polyglutamines. Nature Neuroscience, 2002 Aug, 5(8): 731~6 [20] Zou H, Li Y, Liu X, et al. An Apaf-1 cytochrome C multimeric complex is a functional apoptosome that activates procaspase-9. The Journal of Biological Chemistry, 1999, 274(17): 11549~56 [21] Hu Y, Benedict M A, Ding L, et al. Role of cytochrome C and datp/atp hydrolysis in Apaf-1 mediated caspase-9 activation and apoptosis. The EMBO Journal, 1999, 18(13): 3586~95 [22] Saleh A, Srinivasula S M, Acharya S, et al. Cytochrome C Chemistry, 1997, 272: 21878~2181 [25] Vander Heiden M G, Chandel N S, Li X X, et al. Outer mitochondrial membrane permeability can regulate coupled respiration and cell survival. Proceedings of the National Academy of Sciences of the United States of America, 2000, 97(9):4666~71 [26] Roubertoux P L, Sluyter F, Carlier M, et al. Mitochondrial DNA modifies cognition in interaction with the nuclear genome and age in mice. Nature Genetics, 2003, 35(9): 65~69 [27] Ozawa T. Genetic and functional changes in mitochondria associated with aging. Physiological Reviews Apr, and datp-mediated oligomerization of Apaf-1 is a 77(2): 425~64 prerequisite for procaspase-9 activation. The Journal of Biological Chemistry, 1999, 274(25): 17941~5 [23] Campbell V A. Tetrahydrocannabinol-induced apoptosis of cultured cortical neurones is associated with cytochrome c release and caspase-3 activation. Neuropharmacology Apr, 40(5): 702~9 [24] Adachi S, Cross A R, Babior B M, et al.bcl-2 and the outer mitochondrial membrane in the inactivation of cytochrome c during Fas- mediated apoptosis. The Journal of Biological [28],,. DNA., 2000, 16(6): 535~539 [29] Trifunovic A, Wredenberg A, Falkenberg M, et al. Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature, 2004 May 27, 429(6990): 417~23 [30] Liu J, Atamna H, Kuratsune H, et al. Delaying brain mitochondrial decay and aging with mitochondrial antioxidants and metabolites. ANNALS of the New York Academy of Sciences Apr; 959: 133~66 Mitochondrion And Cognitive Aging Bu Cuiping Xi Gengsi College of Sciences, Shaanxi Normal University, Xi an , Shaanxi, China Abstract: At present, many subjects, such as psychology, biology, sociology, etc, focus their attention on cognitive aging. From the point of view of biology, this paper mainly discussed the relation between the mitochondrion and cognitive aging. The mitochondrion as an important cell organ acts on the cognitive aging in many aspects, such as quantity, distribution, energy supply, Ca 2+ concentrations, nerve cell apoptosis, and mitochondrial gene. When mitochondrial functions are abnormal in the aging course, the cognitive function may be influenced by the negative effects. These investigations may offer useful evidences for understanding the cognitive aging mechanism deeply. Key words: mitochondrion, cognitive aging, Ca 2+, nerve cell apoptosis, mitochondrial gene.