Effects of oral aluminum exposure on behavior and neurogenesis in a transgenic mouse model of Alzheimer's disease

被引:82
作者
Ribes, D. [1 ,2 ,3 ]
Colomina, M. T. [1 ,2 ,3 ]
Vicens, P. [1 ,2 ,3 ]
Domingo, J. L. [3 ]
机构
[1] Univ Rovira & Virgili, Dept Psychol, Tarragona 43007, Spain
[2] Univ Rovira & Virgili, Res Ctr Behav Assessment CRAMC, Tarragona 43007, Spain
[3] Univ Rovira & Virgili, Sch Med, Lab Toxicol & Environm Hlth, E-43201 Reus, Spain
关键词
Aluminum; Alzheimer; Tg; 2576; Neurogenesis; beta-amyloid; Spatial learning; Water maze;
D O I
10.1016/j.expneurol.2008.08.017
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The effects of a very low oral dose of Al on spatial learning and neurogenesis were evaluated in a transgenic mouse (Tg 2576) model of Alzheimer disease. At 5 months of age, wild and Tg 2576 mice received a diet supplemented with Al lactate at 0 and 1 mg/g of diet for 120 days. The experimental groups (n= 7-8) were: control wild, Al-treated wild, control transgenic, and Al-treated transgenic. After 3 months of Al exposure, activity in an open-field and learning in a water maze were evaluated. At the end of the behavioral testing, in order to Study cell proliferation and differentiation in the hippocampus, mice were injected with 5-bromo-2-deoxyuridine (BrdU) and sacrificed 1 or 28 days after the last BrdU injection. Tg 2576 mice were impaired in both acquisition and retention of the water maze task, showing higher amounts of beta-amyloid fragments in brain. Aluminum exposure impaired learning and memory in wild mice and increased the total number of proliferating cells in the dentate gyrus of hippocampus. The low Al doses here experimented Suggest that this element might impair cognition in the general population at closes comparable to current levels of human exposure. Although these doses are not enough to interact with the amyloidogenic pathway, an increase in cell proliferation can indicate a reactive response of the brain to Al insult. Further investigations should be performed to corroborate the effects observed at very low doses of Al and to Study the potential effects derived from a longer exposure period.
引用
收藏
页码:293 / 300
页数:8
相关论文
共 57 条
[1]   AUTORADIOGRAPHIC AND HISTOLOGICAL EVIDENCE OF POSTNATAL HIPPOCAMPAL NEUROGENESIS IN RATS [J].
ALTMAN, J ;
DAS, GD .
JOURNAL OF COMPARATIVE NEUROLOGY, 1965, 124 (03) :319-&
[2]   Disturbance of cerebral function in people exposed to drinking water contaminated with aluminium sulphate: retrospective study of the Camelford water incident [J].
Altmann, P ;
Cunningham, J ;
Dhanesha, U ;
Ballard, M ;
Thompson, J ;
Marsh, F .
BMJ-BRITISH MEDICAL JOURNAL, 1999, 319 (7213) :807-+
[3]   Intra- and intertask relationships in a behavioral test battery given to Tg2576 transgenic mice and controls [J].
Arendash, GW ;
King, DL .
PHYSIOLOGY & BEHAVIOR, 2002, 75 (05) :643-652
[4]   Learning and memory in Transgenic mice Modeling Alzheimer's disease [J].
Ashe, KH .
LEARNING & MEMORY, 2001, 8 (06) :301-308
[5]   Intact spatial learning in adult Tg2576 mice [J].
Bizon, Jennifer ;
Prescott, Sonya ;
Nicolle, Michelle M. .
NEUROBIOLOGY OF AGING, 2007, 28 (03) :440-446
[6]   Aging and neuronal replacement [J].
Brazel, CY ;
Rao, MS .
AGEING RESEARCH REVIEWS, 2004, 3 (04) :465-483
[7]   Restoring production of hippocampal neurons in old age [J].
Cameron, HA ;
McKay, RDG .
NATURE NEUROSCIENCE, 1999, 2 (10) :894-897
[8]   Adult neurogenesis is functionally associated with AD-like neurodegeneration [J].
Chen, Qian ;
Nakajima, Akira ;
Choi, Se Hoon ;
Xiong, Xiaoli ;
Sisodia, Sangram S. ;
Tang, Ya-Ping .
NEUROBIOLOGY OF DISEASE, 2008, 29 (02) :316-326
[9]   Concurrent exposure to aluminum and stress during pregnancy in rats: Effects on postnatal development and behavior of the offspring [J].
Colomina, MT ;
Roig, JL ;
Torrente, M ;
Vicens, P ;
Domingo, JL .
NEUROTOXICOLOGY AND TERATOLOGY, 2005, 27 (04) :565-574
[10]   Modulation of hippocampal cell proliferation, memory, and amyloid plaque deposition in APPsw (Tg2576) mutant mice by isolation stress [J].
Dong, H ;
Goico, B ;
Martin, M ;
Csernansky, CA ;
Bertchume, A ;
Csernansky, JG .
NEUROSCIENCE, 2004, 127 (03) :601-609