PMID- 22912838 OWN - NLM STAT- MEDLINE DCOM- 20130501 LR - 20231105 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 7 IP - 8 DP - 2012 TI - Exercise does not protect against MPTP-induced neurotoxicity in BDNF haploinsufficient mice. PG - e43250 LID - 10.1371/journal.pone.0043250 [doi] LID - e43250 AB - 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. FAU - Gerecke, Kim M AU - Gerecke KM AD - Department of Psychology and Neuroscience Program, Rhodes College, Memphis, Tennessee, United States of America. gereckek@rhodes.edu FAU - Jiao, Yun AU - Jiao Y FAU - Pagala, Viswajeeth AU - Pagala V FAU - Smeyne, Richard J AU - Smeyne RJ LA - eng GR - R01 NS039006/NS/NINDS NIH HHS/United States GR - R01 NS070825/NS/NINDS NIH HHS/United States GR - NS039006/NS/NINDS NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20120817 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (DNA Primers) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*genetics/metabolism MH - DNA Primers/genetics MH - Dopaminergic Neurons/drug effects/*physiology MH - Electrophoresis, Agar Gel MH - Genotype MH - *Haploinsufficiency MH - Immunohistochemistry MH - MPTP Poisoning/physiopathology/*prevention & control MH - Mice MH - Physical Conditioning, Animal/*physiology MH - Proteomics MH - Substantia Nigra/*cytology MH - Tandem Mass Spectrometry PMC - PMC3422268 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2012/08/23 06:00 MHDA- 2013/05/02 06:00 PMCR- 2012/08/17 CRDT- 2012/08/23 06:00 PHST- 2012/04/18 00:00 [received] PHST- 2012/07/18 00:00 [accepted] PHST- 2012/08/23 06:00 [entrez] PHST- 2012/08/23 06:00 [pubmed] PHST- 2013/05/02 06:00 [medline] PHST- 2012/08/17 00:00 [pmc-release] AID - PONE-D-12-11031 [pii] AID - 10.1371/journal.pone.0043250 [doi] PST - ppublish SO - PLoS One. 2012;7(8):e43250. doi: 10.1371/journal.pone.0043250. Epub 2012 Aug 17.