Restoration of MPTP-induced deficits by exercise and Milmed(®) co-treatment

Trevor Archer; Danilo Garcia; Anders Fredriksson

doi:10.7717/peerj.531

Restoration of MPTP-induced deficits by exercise and Milmed(®) co-treatment

PeerJ. 2014 Aug 26:2:e531. doi: 10.7717/peerj.531. eCollection 2014.

Authors

Trevor Archer¹, Danilo Garcia², Anders Fredriksson³

Affiliations

¹ Department of Psychology, University of Gothenburg , Gothenburg , Sweden ; Network for Empowerment and Well-Being , Sweden.
² Network for Empowerment and Well-Being , Sweden ; Institute of Neuroscience and Physiology, Centre for Ethics, Law and Mental Health (CELAM), University of Gothenburg , Gothenburg , Sweden.
³ Department of Neuroscience Psychiatry, Uppsala University , Uppsala , Sweden.

Abstract

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces permanent neurochemical and functional deficits. Following the administration of either two or four injections of the dopamine neurotoxin, MPTP, at a dose of 40 mg/kg, C57/BL6 mice were given access to running-wheels (30-min sessions, four times/week, Monday-Thursday) and treatment with the treated yeast, Milmed(®) (four times/week, Monday-Thursday), or simply running-wheel exercise by itself, over ten weeks. It was observed that the combination of physical exercise and Milmed(®) treatment, the MPTP + Exercise + Yeast (MC) group [MPTP + Exercise + Milmed(®) (MC)], restored spontaneous motor activity markedly by test day 10, restored completely subthreshold L-Dopa-induced activity, and dopamine concentration to 76% of control values, in the condition wherein two administrations of MPTP (2 × 40 mg/kg) were given prior to initiation of exercise and/or Milmed(®) treatment. Physical exercise by itself, MPTP + Exercise (MC) group, attenuated these deficits only partially. Administration of MPTP four times (i.e., 40 mg/kg, s.c., once weekly over four weeks for a total of 160 mg/kg, MPTP + Exercise + Yeast (MC) group [MPTP + Exercise + Milmed(®) (SC)] and MPTP + Exercise (SC), induced a lesioning effect that was far too severe for either exercise alone or the exercise + Milmed(®) combination to ameliorate. Nevertheless, these findings indicate a powerful effect of physical exercise reinforced by Milmed(®) treatment in restoring MPTP-induced deficits of motor function and dopamine neurochemistry in mice.

Keywords: Attenuation; Dopamine; Exercise; Locomotion; MPTP; Milmed®; Parkinsonism; Restoration; Running-wheels; Total activity.

Grants and funding

This research was supported by a grant from Milmed^® AB to Uppsala University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.