Richard J. Smeyne, Ph.D.

Richard J. Smeyne, Ph.D.

Associate Member
Department of Developmental Neurobiology
St. Jude Children's Research Hospital
Affiliated Associate Professor
Department of Anatomy and Neurobiology

Email: Richard J. Smeyne


  • Ph.D. Institution: Thomas Jefferson University, Department of Anatomy, Philadelphia, PA
  • Postdoctoral: Roche Institute of Molecular Biology, Department of Neurosciences, Nutley, NJ


Research Interests

Parkinson's disease is a debilitating neurologic disorder that is characterized by a loss of pigmented neurons in the substantia nigra pars compacta (SNpc) and is probably caused by a multifactorial process involving an interaction of gene effects, subject age, and exposure to an environmental insult. In our lab, we used the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to recapitulate the pathology of human PD in mice. Previously, we found that the C57Bl/6J and SWR/J strains of mice differ in sensitivity to MPTP. By dissecting differences in the genome of these 2 strains of mice, we have identified a single quantitative trait loci (QTL) which theoretically contains the gene(s) that underlie sensitivity to MPTP. This QTL lies within the telomeric end of mChr. 1. We are now in the process of examining the genetic code in this region to uncover the specific genes responsible for MPTP susceptibility. Our lab is also studying which cells (neurons and/or glia) are responsible for the toxicity seen following MPTP administration. Using a novel chimeric culture method, we have found that the genotype of the glial cell plays a crucial role in determining whether an SNpc cell will die after exposure to MPTP. This finding may have implications for the development of novel therapies for the treatment of Parkinson's disease. In addition to discovering the gene(s) and cell types underlying experimental Parkinsonism, we are interested in examining novel methods of neuroprotection. We have found that exposure to an enriched environment (EE) can protect SNpc neurons from MPTP-induced cell death. Using quantitative PCR methods, we have shown that exposure to an EE increases the mRNA levels of BDNF, which has been shown to be neuroprotective in a variety of injury paradigms. In addition to our findings regarding neuroprotection, we have also shown that exposure to an EE can alter the anatomical structure of neurons in various regions of the CNS.

Another project in the lab examines the effects of prenatal exposure to drugs of abuse on developmental brain disorders, including deficits in neuronal and glial cell migration, motor performance, and environmental awareness. Exposure to these drugs in adults has been shown to cause memory defects and disorders of affect. Similar behavioral changes have been observed in animal models of drug abuse. Although the behavioral symptoms of prenatal and adult drug exposure have been described, few studies have examined the developmental mechanisms that underlie these behaviors. Drugs of abuse alter the levels of neurotransmitters in the brain, and changes in neurotransmitter levels can alter cell proliferation, cell migration, formation of neural connections, and cell survival. In the prenatal CNS, cells are generated in ventricular zones and migrate long distances to their final destinations. In the adult CNS, repopulation of neurons is severely limited; however, a few neurons are generated in the subventricular zone of the forebrain and either migrate through the rostral migratory stream to repopulate the olfactory bulb or migrate laterally to repopulate the hippocampus. We are using specific cell markers and computer-aided 3-dimensional reconstruction to trace the developmental migration of these cells. This work will allow us to determine the effects of prenatal or adult exposure to drugs of abuse on the development of the CNS. Related to cell survival, we are examining if mice prenatally exposed to cocaine have an increased sensitivity to drugs, such as MPTP or kainic acid, that effect abnormal release of neurotransmitters and induce cell death.

Representative Publications

  • Gingras S, Earls LR, Howell S, Smeyne RJ, Zakharenko SS, Pelletier S. SCYL2 Protects CA3 Pyramidal Neurons from Excitotoxicity during Functional Maturation of the Mouse Hippocampus. J Neurosci. 2015 Jul 22;35(29):10510-22. doi: 10.1523/JNEUROSCI.2056-14.2015. PubMed PMID: 26203146; PubMed Central PMCID: PMC4510291.
  • Sadasivan S, Zanin M, O'Brien K, Schultz-Cherry S, Smeyne RJ. Induction of microglia activation after infection with the non-neurotropic A/CA/04/2009 H1N1 influenza virus. PLoS One. 2015 Apr 10;10(4):e0124047. doi: 10.1371/journal.pone.0124047. eCollection 2015. PubMed PMID: 25861024; PubMed Central PMCID: PMC4393251.
  • Smeyne M, Sladen P, Jiao Y, Dragatsis I, Smeyne RJ. HIF1α is necessary for exercise-induced neuroprotection while HIF2α is needed for dopaminergic neuron survival in the substantia nigra pars compacta. Neuroscience. 2015 Jun 4;295:23-38. doi: 10.1016/j.neuroscience.2015.03.015. Epub 2015 Mar 19. PubMed PMID: 25796140; PubMed Central PMCID: PMC4524512.
  • Chun S, Westmoreland JJ, Bayazitov IT, Eddins D, Pani AK, Smeyne RJ, Yu J, Blundon JA, Zakharenko SS. Specific disruption of thalamic inputs to the auditory cortex in schizophrenia models. Science. 2014 Jun 6;344(6188):1178-82. doi: 10.1126/science.1253895. PubMed PMID: 24904170; PubMed Central PMCID: PMC4349506.
  • Pani AK, Jiao Y, Sample KJ, Smeyne RJ. Neurochemical measurement of adenosine in discrete brain regions of five strains of inbred mice. PLoS One. 2014 Mar 18;9(3):e92422. doi: 10.1371/journal.pone.0092422. eCollection 2014. PubMed PMID: 24642754; PubMed Central PMCID: PMC3958516.
  • Zigmond MJ, Smeyne RJ. Exercise: is it a neuroprotective and if so, how does it work? Parkinsonism Relat Disord. 2014 Jan;20 Suppl 1:S123-7. doi: 10.1016/S1353-8020(13)70030-0. Review. PubMed PMID: 24262162.

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