Philadelphia University + Thomas Jefferson University


Highlighted Publications

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.

Recent Publications

Mutant LRRK2 mediates peripheral and central immune responses leading to neurodegeneration in vivo

Restoring auditory cortex plasticity in adult mice by restricting thalamic adenosine signaling

Assessment of the effects of MPTP and paraquat on dopaminergic neurons and microglia in the substantia nigra pars compacta of C57BL/6 mice

Erratum: Bacterial Peptidoglycan Traverses the Placenta to Induce Fetal Neuroproliferation and Aberrant Postnatal Behavior (Cell Host and Microbe (2016) 19 (388399))

Bacterial Peptidoglycan Transverses the Placenta to Induce Fetal Neuroproliferation and Aberrant Postnatal Behavior

HIF1α is necessary for exercise-induced neuroprotection while HIF2α is needed for dopaminergic neuron survival in the substantia nigra pars compacta

Induction of microglia activation after infection with the non-neurotropic A/CA/04/2009 H1N1 influenza virus

SCYL2 protects CA3 pyramidal neurons from excitotoxicity during functional maturation of the mouse hippocampus

P75 Regulates Purkinje cell firing by modulating SK channel activity through Rac1

From Man to Mouse: The MPTP Model of Parkinson Disease

Neurochemical measurement of adenosine in discrete brain regions of five strains of inbred mice

Exercise: Is it a neuroprotective and if so, how does it work?

Specific disruption of thalamic inputs to the auditory cortex in schizophrenia models

Immunologic privilege in the central nervous system and the blood-brain barrier

Allopregnanolone Reinstates Tyrosine Hydroxylase Immunoreactive Neurons and Motor Performance in an MPTP-Lesioned Mouse Model of Parkinson's Disease

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

Normal midbrain dopaminergic neuron development and function in miR-133b mutant mice

Long-lasting transcriptional refractoriness triggered by a single exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrimidine

Methylphenidate exposure induces dopamine neuron loss and activation of microglia in the basal ganglia of mice

Inflammatory effects of highly pathogenic H5N1 influenza virus infection in the CNS of mice