Effects of treadmill exercise on behavioral recovery and neural changes in the substantia nigra and striatum of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse

• Published in: Brain research 2011-04, Vol.1386, p.70-80
• Main Authors: Smith, Beth A, Goldberg, Natalie R.S, Meshul, Charles K
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Animals; Biological and medical sciences; Blotting, Western; brain; Corpus Striatum - cytology; Corpus Striatum - metabolism; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dopamine; Dopamine transporter; Exercise; Exercise Test - methods; Exercise Therapy - methods; gait; immunoblotting; immunohistochemistry; Male; Medical sciences; Mice; Mice, Inbred C57BL; MPTP; MPTP Poisoning - pathology; MPTP Poisoning - physiopathology; MPTP Poisoning - rehabilitation; Neural Pathways - cytology; Neural Pathways - metabolism; Neurology; neurons; Organic mental disorders. Neuropsychology; Parkinson's disease; Physical Conditioning, Animal - methods; Presynaptic Terminals - metabolism; Presynaptic Terminals - ultrastructure; protein synthesis; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Recovery of Function - physiology; Substantia Nigra - cytology; Substantia Nigra - metabolism; tyrosine; Tyrosine hydroxylase
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2011.02.003

Abstract Our goal was to extend our understanding of the neural changes behind motor recovery with treadmill exercise in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse. We determined the extent of dopamine (DA) terminal changes using Western immunoblotting [striatal dopamine transporter (DAT) and tyrosine hydroxylase (TH)] and alterations in the mean number of DA cells/section by immunohistochemistry and Nissl staining [TH-labeled cells and thionin-stained cells in the substantia nigra pars compacta (SN-PC)]. We measured recovery of gait performance and amount of spontaneous physical activity using the parallel rod activity chamber (PRAC). We hypothesized that the decrease in TH-labeled neurons in the SN-PC due to MPTP will be partially reversed by treadmill exercise, leading to recovery of motor behavior as measured by the PRAC. Following MPTP or vehicle administration, mice ran on the treadmill for 1 h/day at 18 cm/s, 5 days/week. Results showed that treadmill exercise improves gait performance and increases physical activity while promoting increased protein expression of striatal DAT and TH. Exercise was effective for all mice; however, effects of early treadmill-based intervention appear to have an additional and unique benefit in mice who received MPTP. We are the first to show that, even following a nearly 50% decrease in the mean number of TH-labeled neurons/section in the SN-PC following MPTP, treadmill exercise leads to an increase of neurons in the SN-PC and improved motor behavior.