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Endurance Exercise Confers Neuroprotective Mitochondrial Phenotypes in the Brain of Alzheimer's Disease Mice
Author(s) -
Koo Junghoon,
Kang EunBum,
Kwon InSu,
Jang Yong Chul,
Kim EungJoon,
Lee Youngil,
Cho InHo,
Cho JoonYong
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.1055.35
Subject(s) - neuroprotection , tfam , mitochondrial biogenesis , sirt3 , mitochondrion , genetically modified mouse , microbiology and biotechnology , biology , proteostasis , mptp , transgene , chemistry , endocrinology , biochemistry , nad+ kinase , sirtuin , pharmacology , gene , dopaminergic , dopamine , enzyme
Endurance exercise (EE) is neuroprotective against Alzheimer's Disease (AD). However, the exact mechanisms remain unclear. Here we report that EE preserves cognitive function, increases mitochondrial biogenesis, and provides neuroprotective mitochondrial phenotypes in the brain of transgenic (NSE/APPsw) AD mice. 9‐month‐old mice were assigned to wild type (WT, n=8), transgenic (Tg, n=8), and transgenic exercise (TgE). TgE group performed treadmill EE for 16 weeks (60 min/day at 15m/min). Amyloid β‐42 (Aβ‐42), a hallmark of AD was significantly reduced at both tissue and mitochondria levels in TgE mice compared with Tg mice. NAD dependent deacetylase sirtuins‐1 (SIRT1) is linked to inducing mitochondrial biogenesis and activating α‐secretase responsible for reducing Aβ production. Intriguingly, we observed that EE increased SIRT1 in parallel with mitochondrial biogenesis factors (PGC‐1α, NRF1, TFAM) and proteins (COX‐I and COX‐IV) in TgE mice. In addition, EE downregulated key components of mitochondria permeability transition pore (cyclophilin D, ANT, and VADC). Conversely, TE upregulated mitochondrial transport proteins (TOM20, TOM40, TIM 23) and a chaperone (mHSP70). Moreover, EE increased levels of SIRT3 known to inactivate cyclophilin D in TgE group compared with Tg. Collectively, the present study suggests that the early start EE prior to initiation of AD provides neuroprotective mitochondrial phenotypes against AD and that these phenotypes may possibly be induced by the posttranslational modification of proteins via exercise‐mediated SIRT1/3 activation.