PMID- 29419747 OWN - NLM STAT- MEDLINE DCOM- 20180810 LR - 20220110 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 19 IP - 2 DP - 2018 Feb 8 TI - Voluntary Physical Exercise Improves Subsequent Motor and Cognitive Impairments in a Rat Model of Parkinson's Disease. LID - 10.3390/ijms19020508 [doi] LID - 508 AB - BACKGROUND: Parkinson's disease (PD) is typically characterized by impairment of motor function. Gait disturbances similar to those observed in patients with PD can be observed in animals after injection of neurotoxin 6-hydroxydopamine (6-OHDA) to induce unilateral nigrostriatal dopamine depletion. Exercise has been shown to be a promising non-pharmacological approach to reduce the risk of neurodegenerative disease. METHODS: In this study, we investigated the long-term effects of voluntary running wheel exercise on gait phenotypes, depression, cognitive, rotational behaviors as well as histology in a 6-OHDA-lesioned rat model of PD. RESULTS: We observed that, when compared with the non-exercise controls, five-week voluntary exercise alleviated and postponed the 6-OHDA-induced gait deficits, including a significantly improved walking speed, step/stride length, base of support and print length. In addition, we found that the non-motor functions, such as novel object recognition and forced swim test, were also ameliorated by voluntary exercise. However, the rotational behavior of the exercise group did not show significant differences when compared with the non-exercise group. CONCLUSIONS: We first analyzed the detailed spatiotemporal changes of gait pattern to investigate the potential benefits after long-term exercise in the rat model of PD, which could be useful for future objective assessment of locomotor function in PD or other neurological animal models. Furthermore, these results suggest that short-term voluntary exercise is sufficient to alleviate cognition deficits and depressive behavior in 6-OHDA lesioned rats and long-term treatment reduces the progression of motor symptoms and elevates tyrosine hydroxylase (TH), Brain-derived neurotrophic factor (BDNF), bone marrow tyrosine kinase in chromosome X (BMX) protein expression level without affecting dopaminergic (DA) neuron loss in this PD rat model. FAU - Hsueh, Shih-Chang AU - Hsueh SC AD - The Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan. m105095006@tmu.edu.tw. AD - Center for Neurotrauma and Neuroregeneration, Taipei Medical University, Taipei 11031, Taiwan. m105095006@tmu.edu.tw. FAU - Chen, Kai-Yun AU - Chen KY AD - The Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan. chenkathryn@hotmail.com. AD - Center for Neurotrauma and Neuroregeneration, Taipei Medical University, Taipei 11031, Taiwan. chenkathryn@hotmail.com. FAU - Lai, Jing-Huei AU - Lai JH AD - Center for Neurotrauma and Neuroregeneration, Taipei Medical University, Taipei 11031, Taiwan. m105095006@tmu.edu.tw. AD - Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan. m105095006@tmu.edu.tw. FAU - Wu, Chung-Che AU - Wu CC AD - The Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan. johnwu@tmu.edu.tw. AD - Center for Neurotrauma and Neuroregeneration, Taipei Medical University, Taipei 11031, Taiwan. johnwu@tmu.edu.tw. AD - Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan. johnwu@tmu.edu.tw. AD - Department of Neurosurgery, Taipei Medical University Hospital, Taipei 11031, Taiwan. johnwu@tmu.edu.tw. FAU - Yu, Yu-Wen AU - Yu YW AD - The Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan. yvonneyu524@hotmail.com. AD - Center for Neurotrauma and Neuroregeneration, Taipei Medical University, Taipei 11031, Taiwan. yvonneyu524@hotmail.com. FAU - Luo, Yu AU - Luo Y AD - Department of Neurosurgery, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. yxl710@case.edu. FAU - Hsieh, Tsung-Hsun AU - Hsieh TH AUID- ORCID: 0000-0002-2941-3197 AD - The Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan. hsiehth@mail.cgu.edu.tw. AD - Center for Neurotrauma and Neuroregeneration, Taipei Medical University, Taipei 11031, Taiwan. hsiehth@mail.cgu.edu.tw. AD - Department of Physical Therapy and Graduate Institute of Rehabilitation Science, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan. hsiehth@mail.cgu.edu.tw. FAU - Chiang, Yung-Hsiao AU - Chiang YH AD - The Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan. ychiang@tmu.edu.tw. AD - Center for Neurotrauma and Neuroregeneration, Taipei Medical University, Taipei 11031, Taiwan. ychiang@tmu.edu.tw. AD - Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan. ychiang@tmu.edu.tw. AD - Department of Neurosurgery, Taipei Medical University Hospital, Taipei 11031, Taiwan. ychiang@tmu.edu.tw. LA - eng GR - R01 NS091213/NS/NINDS NIH HHS/United States PT - Journal Article DEP - 20180208 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 7171WSG8A2 (BDNF protein, human) RN - 8HW4YBZ748 (Oxidopamine) RN - EC 1.14.16.2 (Tyrosine 3-Monooxygenase) RN - EC 2.7.1.- (BMX protein, human) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - VTD58H1Z2X (Dopamine) SB - IM MH - Animals MH - Behavior, Animal MH - Brain-Derived Neurotrophic Factor/metabolism MH - *Cognition MH - Disease Models, Animal MH - Dopamine/metabolism MH - Dopaminergic Neurons/metabolism MH - Female MH - Gait MH - *Motor Activity MH - Neuroprotection MH - Oxidopamine/adverse effects MH - Parkinson Disease/etiology/*physiopathology/*psychology/therapy MH - *Physical Exertion MH - Protein-Tyrosine Kinases/genetics/metabolism MH - Rats MH - Substantia Nigra MH - Tyrosine 3-Monooxygenase/metabolism PMC - PMC5855730 OTO - NOTNLM OT - 6-hydroxydopamine OT - Parkinson's disease OT - neuroprotection OT - voluntary physical exercise COIS- The authors declare no conflict of interest. EDAT- 2018/02/09 06:00 MHDA- 2018/08/11 06:00 PMCR- 2018/02/01 CRDT- 2018/02/09 06:00 PHST- 2017/12/28 00:00 [received] PHST- 2018/01/19 00:00 [revised] PHST- 2018/02/02 00:00 [accepted] PHST- 2018/02/09 06:00 [entrez] PHST- 2018/02/09 06:00 [pubmed] PHST- 2018/08/11 06:00 [medline] PHST- 2018/02/01 00:00 [pmc-release] AID - ijms19020508 [pii] AID - ijms-19-00508 [pii] AID - 10.3390/ijms19020508 [doi] PST - epublish SO - Int J Mol Sci. 2018 Feb 8;19(2):508. doi: 10.3390/ijms19020508.