Exercise does not protect against MPTP-induced neurotoxicity in BDNF haploinsufficient mice.
Exercise has been demonstrated to potently protect substantia nigra pars compacta (SN) dopaminergic neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity. One mechanism proposed to account for this neuroprotection is the upregulation of neurotrophic factors. Several neurotrophic factors, including Brain Derived Neurotrophic Factor (BDNF), have been shown to upregulate in response to exercise. In order to determine if exercise-induced neuroprotection is dependent upon BDNF, we compared the neuroprotective effects of voluntary exercise in mice heterozygous for the BDNF gene (BDNF+/-) with strain-matched wild-type (WT) mice. Stereological estimates of SNpc DA neurons from WT mice allowed 90 days exercise via unrestricted running demonstrated complete protection against the MPTP-induced neurotoxicity. However, BDNF+/- mice allowed 90 days of unrestricted exercise were not protected from MPTP-induced SNpc DA neuron loss. Proteomic analysis comparing SN and striatum from 90 day exercised WT and BDNF+/- mice showed differential expression of proteins related to energy regulation, intracellular signaling and trafficking. These results suggest that a full genetic complement of BDNF is critical for the exercise-induced neuroprotection of SNpc DA neurons.
Department of Psychology and Neuroscience Program, Rhodes College, Memphis, Tennessee, United States of America. gereckek@rhodes.edu
Kim M
KM
Gerecke
Yun
Y
Jiao
Viswajeeth
V
Pagala
Richard J
RJ
Smeyne
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000502:physiology*; D004587:Electrophoresis, Agar Gel; D005838:Genotype; D057895:Haploinsufficiency; D007150:Immunohistochemistry; D020267:MPTP Poisoning / Q000503:physiopathology / Q000517:prevention & control*; D051379:Mice; D010805:Physical Conditioning, Animal / Q000502:physiology*; D040901:Proteomics; D013378:Substantia Nigra / Q000166:cytology*; D053719:Tandem Mass Spectrometry
D019208:Brain-Derived Neurotrophic Factor; D017931:DNA Primers