Sadasivan, S., Sharp, B. Schultz-Cherry, S.A. and Smeyne, RJ. 2017. Synergistic effects of influenza and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can be eliminated by the use of influenza therapeutics: Experimental evidence for the multi-hit hypothesis. npj Parkinson’s Disease. Online. doi: 10.1038/s41531-017-0019-z. PMID: 28649618.

In this paper, we show that mice infected with a strain of Type A influenza that is circulating among humans today (H1N1) can synergize with environmental agents to increase the risk for development of Parkinson’s disease. We highlight two important finding.  First, this synergistic effect can occur long after the influenza infection has resolved. Second, we show that vaccination against the virus, or antiviral medications such as Tamiflu administered at the time of infection prevented this synergism.

Smeyne, M., Sladen, P., Jiao, Y., Dragatsis, I., Smeyne, R.J. 2015. HIF1alpha is Necessary for Exercise-Induced Neuroprotection while HIF2alpha is Needed for Dopaminergic Neuron Survival in the Substantia Nigra pars compacta. Neuroscience, 295:23-38. PMID: 25796140.

In this paper, we show that the induction of hypoxia in dopaminergic neurons of the substantia nigra is critical for the induction of exercise-induced neuroprotection. We also show, using a conditional knockout protocol, that the expression of the transcription factor, Hypoxia Inducing Factor 1alpha (HIF1alpha) in these cells is critical for this exercise mediated neuroprotection. 

Faherty CJ, Shepherd KR, Herasimtschuk A and Smeyne RJ. 2005. Environmental enrichment eliminates neuronal death in experimental Parkinsonism. Mol Brain Res 134: 170-179. PMID: 15790541 and Gerecke KM, Jiao Y, Pani A, Pagala V, Smeyne RJ. 2010. Exercise protects against MPTP-induced neurotoxicity in mice. Brain Res. 1341:72-83. PMID: 20116369

In these papers, we show that the 3 months of environmental enrichment or exercise alone can protect dopaminergic neurons in the substantia nigra pars compacta from MPTP-induced parkinsonism. This was the critical work that showed an animals housing condition could: 1) affect its susceptibility to environmental toxins and 2) showed that exercise was a critical part of this neuroprotective environment. This preclinical work lead to the (now standard) use of exercise as a treatment modality in patients diagnosed with Parkinson’s disease.