成年海马神经再生与阿尔茨海默病关系的研究进展

摘要/Abstract

摘要： 海马神经再生持续于哺乳动物整个成年期。在生理刺激以及脑外伤等病理因素的刺激下，神经干细胞可发生增殖、迁移、分化，最终整合到神经元网络中。阿尔茨海默病（Alzheimer^,s disease，AD）是一种中枢神经系统退行性疾病，主要病理学特征为细胞内外β淀粉样蛋白（β-amyloid peptide, Aβ）沉积、细胞内神经原纤维缠结（neurofibrillary tangles, NFT），以及由这些引发的神经元变性、坏死。目前，应用海马神经再生治疗AD已成为极具潜力的治疗手段。该文综述了最近成年海马神经再生与AD关系的研究进展。

关键词: 海马, 神经再生, 阿尔茨海默病

Abstract: Neurogenesis occurs throughout the adulthood in mammals, which involves neural stem cell proliferation, migration, differentiation and integration into the circuits. Alzheimer's disease (AD) is a progressive neurodegenerative disorder, characterized in the brain by amyloid plaque deposits, neurofibrillary tangles and neuronal loss. In recent years, evidence indicates that adult hippocampal neurogenesis provides new opportunities for the treatment for AD. Here we review recent progress on the relationship between adult hippocampal neurogenesis and AD.

Key words: hippocampus, neurogenesis, Alzheimer's disease

中图分类号:

R338

何娜，殷明，王泽剑. 成年海马神经再生与阿尔茨海默病关系的研究进展[J]. 神经药理学报, 2013, 3(6): 25-32.

HE Na, YIN Ming, WANG Ze-jian. Progress in the Relationship of Adult Hippocampal Neurogenesis and Alzheime’s Disease[J]. Acta Neuropharmacologica, 2013, 3(6): 25-32.

参考文献

[1] Ming Guo-li, Song Hong-jun. Adult neurogenesis in the mammalian brain: significant answers and significant questions [J]. Neuron, 2011, 70(4): 687-702.

[2] Paul M Thompson, Kiralee M Hayashi, Rebecca A Dutton, et al. Tracking Alzheimer's disease [J]. Ann N Y Acad Sci, 2007, 1097: 183-214.

[3] Lorena Varela-Nallar, Florencia C Aranguiz, Ana C Abbott, et al. Adult hippocampal neurogenesis in aging and Alzheimer's disease [J]. Birth Defects Research Part C: Embryo Today: Reviews, 2010, 90(4): 284-296.

[4] Mu Yang-ling, Fred H Gage. Adult hippocampal neurogenesis and its role in Alzheimer's disease [J]. Molecular Neurodegeneration, 2011, 6(1): 85.

[5] Jose J Rodriguez, Victoria C Jones, M Tabuchi, et al. Impaired adult neurogenesis in the dentate gyrus of a triple transgenic mouse model of Alzheimer's disease [J]. PLoS One, 2008, 3(8): e2935.

[6] Zhao Chun-mei, Wei Deng, Fred H Gage. Mechanisms and functional implications of adult neurogenesis [J]. Cell, 2008, 132(4): 645-660.

[7] Lorena Varela-Nallar, Florencia C Aranguiz, Ana C Abbott, et al. Adult hippocampal neurogenesis in aging and Alzheimer's disease [J]. Birth Defects Res C Embryo Today, 2010, 90(4): 284-296.

[8] Nagy Z, M M Esiri, A D Smith. Expression of cell division markers in the hippocampus in Alzheimer's disease and other neurodegenerative conditions [J]. Acta Neuropathol, 1997, 93(3): 294-300.

[9] Jin Kun-lin, Alyson L Peel, Xiao Ou Mao, et al. Increased hippocampal neurogenesis in Alzheimer's disease [J]. Proc Natl Acad Sci USA, 2004, 101(1): 343-347.

[10] Li Bin, Hidenaga Yamamori, Yoshitaka Tatebayashi, et al. Failure of neuronal maturation in Alzheimer disease dentate gyrus [J]. J Neuropathol Exp Neurol, 2008, 67(1): 78-84.

[11] Mark A Lovell, Hartmut Geiger, Gary E Van Zant, et al. Isolation of neural precursor cells from Alzheimer's disease and aged control postmortem brain [J]. Neurobiology of Aging, 2006, 27(7): 909-917.

[12] Karin Boekhoorn, Marian Joels, Paul J Lucassen. Increased proliferation reflects glial and vascular-associated changes, but not neurogenesis in the presenile Alzheimer hippocampus [J]. Neurobiol Dis, 2006, 24(1): 1-14.

[13] Robert Diaz Brinton, Wang Jun-ming. Therapeutic potential of neurogenesis for prevention and recovery from Alzheimer's disease: allopregnanolone as a proof of concept neurogenic agent [J]. Curr Alzheimer Res, 2006, 3(3): 185-190.

[14] Iryna Ziabreva, Elaine Perry, Robert Perry, et al. Altered neurogenesis in Alzheimer's disease [J]. J Psychosom Res, 2006, 61(3): 311-316.

[15] Leslie Crews, Anthony Adame, Christina Patrick, et al. Increased BMP6 levels in the brains of Alzheimer's disease patients and APP transgenic mice are accompanied by impaired neurogenesis [J]. J Neurosci, 2010, 30(37): 12252-12262.

[16] Michael H Donovan, Umar Yazdani, Rebekah D Norris, et al. Decreased adult hippocampal neurogenesis in the PDAPP mouse model of Alzheimer's disease [J]. J Comp Neurol, 2006, 495(1): 70-83.

[17] Norman J Haughey, Avi Nath, Sic L Chan, et al. Disruption of neurogenesis by amyloid beta-peptide, and perturbed neural progenitor cell homeostasis, in models of Alzheimer's disease [J]. J Neurochem, 2002, 83(6): 1509-1524.

[18] David R Borchelt, Janine Davis, Marek Fischer, et al. A vector for expressing foreign genes in the brains and hearts of transgenic mice [J]. Genet Anal, 1996, 13(6): 159-163.

[19] Sara Baratchi, Jane Evans, Warren P Tate, et al. Secreted amyloid precursor proteins promote proliferation and glial differentiation of adult hippocampal neural progenitor cells [J]. Hippocampus, 2012, 22(7): 1517-1527.

[20] Sebastian Mirochnic, Susanne Wolf, Matthias Staufenbiel, et al. Age effects on the regulation of adult hippocampal neurogenesis by physical activity and environmental enrichment in the APP23 mouse model of Alzheimer disease [J]. Hippocampus, 2009, 19(10): 1008-1018.

[21] Florian V Ermini, Stefan Grathwohl, Rebecca Radde, et al. Neurogenesis and alterations of neural stem cells in mouse models of cerebral amyloidosis [J]. Am J Pathol, 2008, 172(6): 1520-1528.

[22] Jin Kun-lin, Veronica Galvan, Xie Lin, et al. Enhanced neurogenesis in Alzheimer's disease transgenic (PDGF-APPSw,Ind) mice [J]. Proc Natl Acad Sci USA, 2004, 101(36): 13363-13367.

[23] Miguel A Lopez-Toledano, Michael L Shelanski. Increased neurogenesis in young transgenic mice overexpressing human APP(Sw, Ind) [J]. J Alzheimers Dis, 2007, 12(3): 229-240.

[24] Gan Li, Qiao Shu-hong, Lan Xun, et al. Neurogenic responses to amyloid-beta plaques in the brain of Alzheimer's disease-like transgenic (pPDGF-APPSw,Ind) mice [J]. Neurobiol Dis, 2008, 29(1): 71-80.

[25] Radek Kolecki, Giuseppe Lafauci, Richard Rubenstein, et al. The effect of amyloidosis-beta and ageing on proliferation of neuronal progenitor cells in APP-transgenic mouse hippocampus and in culture [J]. Acta Neuropathol, 2008, 116(4): 419-424.

[26] Paul H Wen, Patrick R Hof, Chen Xiao-ping, et al. The presenilin-1 familial Alzheimer disease mutant P117L impairs neurogenesis in the hippocampus of adult mice [J]. Exp Neurol, 2004, 188(2): 224-237.

[27] Nathalie L Chevallier, Salvador Soriano, David E Kang, et al. Perturbed neurogenesis in the adult hippocampus associated with presenilin-1 A246E mutation [J]. Am J Pathol, 2005, 167(1): 151-159.

[28] Hu Yuan-shih, Xu Peng, Gustavo Pigino, et al. Complex environment experience rescues impaired neurogenesis, enhances synaptic plasticity, and attenuates neuropathology in familial Alzheimer's disease-linked APPswe/PS1DeltaE9 mice [J]. FASEB J, 2010, 24(6): 1667-1681.

[29] Barbara Biscaro, Olle Lindvall, Christoph Hock, et al. Abeta immunotherapy protects morphology and survival of adult-born neurons in doubly transgenic APP/PS1 mice [J]. J Neurosci, 2009, 29(45): 14108-14119.

[30] Yu Ying-xin, He Jue, Zhang Yan-bo, et al. Increased hippocampal neurogenesis in the progressive stage of Alzheimer's disease phenotype in an APP/PS1 double transgenic mouse model [J]. Hippocampus, 2009, 19(12): 1247-1253.

[31] Laure Verret, Joanna L Jankowsky, Guilian M Xu, et al. Alzheimer's-type amyloidosis in transgenic mice impairs survival of newborn neurons derived from adult hippocampal neurogenesis [J]. J Neurosci, 2007, 27(25): 6771-6780.

[32] Zhang Chen, Elizabeth McNeil, Lindsay Dressler, et al. Long-lasting impairment in hippocampal neurogenesis associated with amyloid deposition in a knock-in mouse model of familial Alzheimer's disease [J]. Experimental Neurology, 2007, 204(1): 77-87.

[33] N Taniuchi, T Niidome, Y Goto, et al. Decreased proliferation of hippocampal progenitor cells in APPswe/PS1dE9 transgenic mice [J]. Neuroreport, 2007, 18(17): 1801-1805.

[34] Michael Demars, Yuan-Shih Hu, Archana Gadadhar, et al. Impaired neurogenesis is an early event in the etiology of familial Alzheimer's disease in transgenic mice [J]. J Neurosci Res, 2010, 88(10): 2103-2117.

[35] Maria Becker, Vered Lavie, Beka Solomon. Stimulation of endogenous neurogenesis by anti-EFRH immunization in a transgenic mouse model of Alzheimer's disease [J]. Proc Natl Acad Sci USA, 2007, 104(5): 1691-1696.

[36] Nibaldo C Inestrosa, E Arenas. Emerging roles of Wnts in the adult nervous system [J]. Nat Rev Neurosci, 2010, 11(2): 77-86.

[37] Nibaldo C Inestrosa, Carla Montecinos-Oliva, Marco Fuenzalida. Wnt Signaling: Role in Alzheimer Disease and Schizophrenia [J]. J Neuroimmune Pharmacol, 2012, 7(4): 788-807.

[38] Wu Qian, Li Yi, Xiao Bo. DISC1-related signaling pathways in adult neurogenesis of the hippocampus [J]. Gene, 2013, 518(2): 223-230.

[39] Itaru Imayoshi, Ryoichiro Kageyama. The Role of Notch Signaling in Adult Neurogenesis [J]. Molecular Neurobiology, 2011, 44(1): 7-12.

[40] Wang Yue, Sic L Chan, Lucio Miele, et al. Involvement of Notch signaling in hippocampal synaptic plasticity [J]. Proc Natl Acad Sci USA, 2004, 101(25): 9458-9462.

[41] Joshua J Breunig, John Silbereis, Flora M Vaccarino, et al. Notch regulates cell fate and dendrite morphology of newborn neurons in the postnatal dentate gyrus [J]. Proc Natl Acad Sci USA, 2007, 104(51): 20558-20563.

[42] Rui M Costa, Tasuku Honjo, Alcino J Silva. Learning and memory deficits in Notch mutant mice [J]. Curr Biol, 2003, 13(15): 1348-1354.

[43] O Berezovska, P McLean, R Knowles, et al. Notch1 inhibits neurite outgrowth in postmitotic primary neurons [J]. Neuroscience, 1999, 93(2): 433-439.

[44] Woo H-N, J-S Park, AR Gwon, et al. Alzheimer’s disease and Notch signaling [J]. Biochem Biophys Res Commun, 2009, 390(4): 1093-1097.

[45] Eun Kyung Kim, Eui-Ju Choi. Pathological roles of MAPK signaling pathways in human diseases [J]. Biochimica Biophysica Acta, 2010, 1802(4): 396-405.

[46] Norifumi Shioda, Han Feng, Kohji Fukunaga. Role of Akt and ERK signaling in the neurogenesis following brain ischemia [J]. Int Rev Neurobiol, 2009, 85: 375-387.

[47] Neil M Fournier, Boyoung Lee, Mounira Banasr, et al. Vascular endothelial growth factor regulates adult hippocampal cell proliferation through MEK/ERK- and PI3K/Akt-dependent signaling [J]. Neuropharmacology, 2012, 63(4): 642-652.

[48] Tania R Benedetti, Lucelia Justino Borges, Edio Luiz Petroski, et al. [Physical activity and mental health status among elderly people] [J]. Rev Saude Publica, 2008, 42(2): 302-307.

[49] M Hasan Mohajeri, Genevieve Leuba. Prevention of age-associated dementia [J]. Brain Res Bull, 2009, 80(4-5): 315-325.

[50] Arne Herring, Oliver Ambree, Manuel Tomm, et al. Environmental enrichment enhances cellular plasticity in transgenic mice with Alzheimer-like pathology [J]. Exp Neurol, 2009, 216(1): 184-192.

[51] J J Rodriguez, H N Noristani, M Olabarria, et al. Voluntary running and environmental enrichment restores impaired hippocampal neurogenesis in a triple transgenic mouse model of Alzheimer's disease [J]. Curr Alzheimer Res, 2011, 8(7): 707-717.

[52] Jenna C Carroll, Emily R Rosario, Lilly Chang, et al. Progesterone and estrogen regulate Alzheimer-like neuropathology in female 3xTg-AD mice [J]. J Neurosci, 2007, 27(48): 13357-13365.

[53] L Santarelli, M Saxe, C Gross, et al. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants [J]. Science, 2003, 301(5634): 805-809.

[54] H N Noristani, M Olabarria, A Verkhratsky, et al. Serotonin fibre sprouting and increase in serotonin transporter immunoreactivity in the CA1 area of hippocampus in a triple transgenic mouse model of Alzheimer's disease [J]. Eur J Neurosci, 2010, 32(1): 71-79.

[55] Stefano Pluchino, Lucia Zanotti, Barbara Rossi, et al. Neurosphere-derived multipotent precursors promote neuroprotection by an immunomodulatory mechanism [J]. Nature, 2005, 436(7048): 266-271.

[56] Mathew Blurton-Jones, Masashi Kitazawa, Hilda Martinez-Coria, et al. Neural stem cells improve cognition via BDNF in a transgenic model of Alzheimer disease [J]. Proc Natl Acad Sci USA, 2009, 106(32): 13594-13599.

[57] Kimberly Christian, Hong Song, Ming Guo-li. Adult neurogenesis as a cellular model to study schizophrenia [J]. Cell Cycle, 2010, 9(4): 636-637.

[58] Laura Cancedda, Hubert Fiumelli, Karen Chen, et al. Excitatory GABA action is essential for morphological maturation of cortical neurons in vivo [J]. J Neurosci, 2007, 27(19): 5224-5235.

[59] Amelia Marutle, Masao Ohmitsu, Mats Nilbratt, et al. Modulation of human neural stem cell differentiation in Alzheimer (APP23) transgenic mice by phenserine [J]. Proc Natl Acad Sci USA, 2007, 104(30): 12506-12511.