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The Effect of Treadmill Exercise on Tau Hyperphosphorylayion in an Aged Transgenic Mouse Model of Taupathies

  • Wang, Seong-Hwan (Exercise Biochemistry Laboratory, Korea National Sport University) ;
  • Kang, Eun-Bum (Exercise Biochemistry Laboratory, Korea National Sport University) ;
  • Kwon, In-Su (Exercise Biochemistry Laboratory, Korea National Sport University) ;
  • Koo, Jung-Hoon (Exercise Biochemistry Laboratory, Korea National Sport University) ;
  • Shin, Kwang-O (Exercise Biochemistry Laboratory, Korea National Sport University) ;
  • Jang, Yong-Chul (Exercise Biochemistry Laboratory, Korea National Sport University) ;
  • Um, Hyun-Sub (Department of Exercise prescription, Kon-Yang University) ;
  • Oh, Yoo-Sung (Department of Sport Informatics, University of Seoul) ;
  • Kim, Chul-Hyun (Exercise Biochemistry Laboratory, Korea National Sport University) ;
  • Cho, In-Ho (Exercise Biochemistry Laboratory, Korea National Sport University) ;
  • Cho, Joon-Yong (Exercise Biochemistry Laboratory, Korea National Sport University)
  • Received : 2012.06.13
  • Published : 2012.06.30

Abstract

Alzheimer's disease (AD) is the most common cause of dementia in adults. Microtubule associated protein tau is abnormally phosphorylated in AD and aggregates as paired helical filaments (PHFs) in neurofibrillary tangles (NFTs). NFTs are the most common intraneuronal inclusion in the brains of patients with AD and have been implicated in mediating neuronal cell death and cognitive deficit. Aberrant phosphorylation of tau is an early pathological event in AD, but the underlying mechanisms are unclear. MAP kinases are a family of Serine/Threonine (Ser/Thr) kinases that involved hyper - phosphorylation of tau in AD. The purpose of this study was to investigate the effect of treadmill exercise on phosphorylation of tau level and activation of MAPKs including JNK, ERK, p38-MAPK. To address this, Tg mouse model of AD, Tg-NSE/hTau 23, which expresses human tau 23 in the brain, was chosen. Animals were subjected to treadmill exercise for 12 weeks from 24 months of age. Treadmill exercise in Tg group improved cognitive function compared with Tg-SED group in watermaze test. In addition, treadmill exercised Tg mice significantly reduced the activation of JNK54/46, p38-MAPK and tau (Ser404, Ser202, Thr231), and increased activation of ERK44/42 in cerebral cortex. These results suggest that treadmill exercise may provide a therapeutic potential to alleviate the tau pathology like AD.

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