HSV-mediated delivery of erythropoietin restores dopaminergic function in MPTP-treated mice

Mol Ther. 2006 Nov;14(5):710-5. doi: 10.1016/j.ymthe.2006.07.004. Epub 2006 Sep 1.

Abstract

To investigate the neuroprotective effects of erythropoietin (EPO) in a rodent model of Parkinson disease, we inoculated a nonreplicating herpes simplex virus-based vector expressing EPO (vector DHEPO) into the striatum of mice 1 week prior to, or 2 weeks after, the start of continual administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (4 mg/kg intraperitoneally, 5 of 7 days) for 6 weeks. Inoculation with DHEPO prior to MPTP intoxication preserved behavioral function measured by pellet retrieval and the histological markers of tyrosine hydroxylase-immunoreactive (TH-IR) neuronal cell bodies in the substantia nigra (SN) and TH-IR and dopamine transporter-immunoreactive (DAT-IR) terminals in striatum. Inoculation of DHEPO 2 weeks into a 6-week course of MPTP resulted in improvement of behavioral function and restoration of TH-IR cells in SN and TH- and DAT-IR in the striatum. The effects of vector-produced EPO were similar in magnitude to the effects of vector-mediated expression of glial-derived neurotrophic factor in the same model. These results demonstrate that vector-mediated EPO production may be used to reverse dopaminergic neurodegeneration in the face of continued toxic insult.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology*
  • Animals
  • Brain / metabolism
  • Dopamine / metabolism*
  • Erythropoietin / genetics*
  • Erythropoietin / metabolism*
  • Female
  • Genetic Vectors / genetics
  • Mice
  • Mice, Inbred C57BL
  • Simplexvirus / genetics*

Substances

  • Erythropoietin
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Dopamine