Fingolimod increases brain-derived neurotrophic factor levels and ameliorates amyloid β-induced memory impairment

被引：96

作者：

Fukumoto, Kazuya ^{[1
]}

Mizoguchi, Hiroyuki ^{[1
]}

Takeuchi, Hideyuki ^{[2
]}

Horiuchi, Hiroshi ^{[2
]}

Kawanokuchi, Jun ^{[2
]}

Jin, Shijie ^{[2
]}

Mizuno, Tetsuya ^{[2
]}

Suzumura, Akio ^{[2
]}

机构：

[1] Nagoya Univ, Environm Med Res Inst, Futurist Environm Simulat Ctr, Chikusa Ku, Nagoya, Aichi 4648601, Japan

[2] Nagoya Univ, Environm Med Res Inst, Dept Neuroimmunol, Chikusa Ku, Nagoya, Aichi 4648601, Japan

来源：

BEHAVIOURAL BRAIN RESEARCH | 2014年 / 268卷

基金：

日本学术振兴会;

关键词：

Fingolimod; Alzheimer's disease; Amyloid beta; Brain-derived neurotrophic factor; CENTRAL-NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; FULL-LENGTH; OXIDATIVE STRESS; RAT HIPPOCAMPUS; MESSENGER-RNA; BDNF LEVELS; FTY720; TRKB; MODEL;

D O I：

10.1016/j.bbr.2014.03.046

中图分类号：

B84 [心理学]; C [社会科学总论]; Q98 [人类学];

学科分类号：

03 ; 0303 ; 030303 ; 04 ; 0402 ;

摘要：

Alzheimer's disease is a progressive neurodegenerative disorder. Amyloid beta, a neurotoxic protein, causes disruption of hippocampal synaptic plasticity, and induces cognitive impairment in Alzheimer's disease. We previously. revealed that fingolimod, a new oral immunosuppressant used to treat multiple sclerosis, ameliorates oligomeric amyloid beta-induced neuronal damage via up-regulation of neuronal brain-derived neurotrophic factor (BDNF). Here, we showed that oral administration of fingolimod ameliorated the impairment in object recognition memory and associative learning in mice injected with amyloid beta. This effect was associated with restoration of normal BDNF expression levels in the cerebral cortices and hippocampi, suggesting that neuroprotection was mediated by up-regulation of neuronal BDNF levels. Therefore, fingolimod may provide therapeutic effects in patients with Alzheimer's disease. (C) 2014 Elsevier B.V. All rights reserved.

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页码：88 / 93

页数：6

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