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Comparative Study
. 2012;7(8):e43250.
doi: 10.1371/journal.pone.0043250. Epub 2012 Aug 17.

Exercise does not protect against MPTP-induced neurotoxicity in BDNF haploinsufficient mice

Kim M Gerecke  1 , Yun Jiao, Viswajeeth Pagala, Richard J Smeyne
Affiliations
Comparative Study

Exercise does not protect against MPTP-induced neurotoxicity in BDNF haploinsufficient mice

Kim M Gerecke et al. PLoS One. 2012.

Abstract

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Representative gel of PCR products for genotyping.
WT animals were identified by the presence of one band at ∼275 base pairs, while BDNF+/− mice were identified by the presence of both the ∼275 base pair band and a unique band at ∼340 base pairs.
Figure 2
Figure 2. WT and BDNF+/− mice do not differ in the amount of running.
Average total running activity for WT and BDNF+/− mice during the (A) daytime, (B) nighttime or (C) the total 24 hour interval. (D) The average total running distance for WT and BDNF+/− mice at 30 day intervals. Bars indicate the average of total running activity ± SEM.
Figure 3
Figure 3. WT and BDNF+/− mice do not differ in the pattern of running.
The pattern of average running activity for mice over the duration of the 90-day experimental period. Points represent the average total running activity for WT or BDNF+/− mice for each 24 hour period ± SEM.
Figure 4
Figure 4. Exercise does not protect against MPTP-induced SN DA neurotoxicity in BDNF +/− mice.
(A) Representative photomicrograph of the SNpc of C57BL/6 mouse at the level of the medial longitundinal fasciculus (mlf). (B) Representative photomicrograph of the SNpc of BDNF+/− mouse at the level of the medial longitundinal fasciculus (mlf). (C) Representative photomicrograph of the SNpc of the C57BL/6 mouse 7 days following MPTP mouse at the level of the mlf. (D) Representative photomicrograph of the SNpc of the BDNF+/− mouse allowed 3 months exercise and then treated with MPTP. There is no difference in the appearance of the sedentary MPTP-treated C57BL/6 mouse and the BDNF+/− mouse allowed exercise. (E) BDNF+/− mice allowed free access to running wheels for 90 days prior to MPTP administration lost significantly greater SN DA neurons than exercising WT littermates. Bars represent the average ± SEM; * p<0.01 as compared to WT SH+Sal; + p<0.01 as compared to WT Ex+MPTP.
See this image and copyright information in PMC

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