Fingolimod increases brain-derived neurotrophic factor levels and ameliorates amyloid β-induced memory impairment.
Alzheimer's disease is a progressive neurodegenerative disorder. Amyloid β, 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 β-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 β. 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.
Futuristic Environmental Simulation Center, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
Kazuya
K
Fukumoto
Futuristic Environmental Simulation Center, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan. Electronic address: h-mizo@riem.nagoya-u.ac.jp.
Hiroyuki
H
Mizoguchi
Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
Hideyuki
H
Takeuchi
Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
Hiroshi
H
Horiuchi
Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
Jun
J
Kawanokuchi
Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
Shijie
S
Jin
Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
Tetsuya
T
Mizuno
Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
Akio
A
Suzumura
D000544:Alzheimer Disease; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001245:Association Learning / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D000068876:Fingolimod Hydrochloride; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000633:toxicity*; D011409:Propylene Glycols / Q000494:pharmacology*; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015854:Up-Regulation
D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D011409:Propylene Glycols; C075222:amyloid beta-protein (1-42); D000068876:Fingolimod Hydrochloride; D013110:Sphingosine
Alzheimer's disease; Amyloid β; Brain-derived neurotrophic factor; Fingolimod