Objective: To increase our understanding of how physical exercise may drive adaptive neuroplasticity in a mouse model of Parkinson’s disease (PD).

Background: PD is a common and incapacitating neurodegenerative disease, without curative treatment. Pathologically, PD is characterized by progressive neuronal loss in dopaminergic brain areas, while dysfunction of non-dopaminergic pathways emerges in advanced stages of the disease. It has been suggested that physical exercise promotes adaptive neuroplasticity and as such may compensate for the loss of function due to neurodegeneration, but many aspects of these mechanisms remain unclear.

Methods: Six months old C57BL6 mice were i.p. injected with MPTP (70 mg/kg, 4 injections, 2 hrs interval), to induce partial destruction of nigrostriatal dopaminergic neurons. After a 2-week recovery period, cohorts of treated and untreated animals received an exercise program (28 days of forced treadmill running for 30 minutes twice a day). mRNA expression profiles from substantia nigra (SN), ventral tegmental area (VTA) and their dorsolateral (DL) and ventromedial (VM) striatal target areas were obtained by RNAseq, and compared with control groups without exercise. Enriched gene categories among differentially expressed mRNAs were identified using the Ingenuity pathway analysis software package (www.ingenuity.com).

Results: Preliminary results indicate that the molecular pathways affected by forced exercise overlap with those affected by MPTP. Upstream regulators of these pathways include levodopa (dopamine precursor; in SN and VM) and RICTOR (a key subunit of the mTORC2 complex that has been implicated in dopamine signaling; in VTA and DL), suggesting that these pathways are relevant for PD. Of note, exercise does not always counteract the MPTP effects (e.g. in the VM striatum). We constructed molecular landscapes that harbor the specific molecular interactions affected by forced physical exercise in MPTP-treated mice.

Conclusions: Based on these preliminary findings, the effects of forced physical exercise in the MPTP mouse model of PD at the molecular level appear intricate, may depend on neuroanatomical substrate and not be always beneficial. These results may serve as the basis for the development and optimization of novel exercise-related disease-modifying strategies that aim at enhancing compensatory adaptive neuroplasticity in PD.

Some of these data have been presented at AD/PD 2015.

« Back to 2016 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/exercise-induced-adaptive-neuroplasticity-in-the-mptp-mouse-model-of-parkinsons-disease/