Glatiramer Acetate Reverses Motor Dysfunction and the Decrease in Tyrosine Hydroxylase Levels in a Mouse Model of Parkinson's Disease

Madeline J. Churchill, Mark A. Cantu, Ella A. Kasanga, C. Moore, Michael Francis Salvatore, Charles K. Meshul

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease and there are no effective treatments that either slow or reverse the degeneration of the dopamine (DA) pathway. Using a 4-week progressive MPTP (1-methyl-1,2,3,6-tetrahydropyridine) neurotoxin model of PD, which is characterized by neuroinflammation, loss of nigrostriatal DA, and motor dysfunction, as seen in patients with PD, we tested whether post-MPTP treatment with glatiramer acetate (GA), an immunomodulatory drug, could reverse these changes. GA restored the grip dysfunction and gait abnormalities that were evident in the MPTP treated group. The reversal of the motor dysfunction was attributable to the substantial recovery in tyrosine hydroxylase (TH) protein expression in the striatum. Within the substantia nigra pars compacta, surface cell count analysis showed a slight increase in TH + cells following GA treatment in the MPTP group, which was not statistically different from the vehicle (VEH) group. This was associated with the recovery of BDNF (brain derived neurotrophic factor) protein levels and a reduction in the microglial marker, IBA1, protein expression within the midbrain. Alpha synuclein (syn-1) levels within the midbrain and striatum were decreased following MPTP, while GA facilitated recovery to VEH levels in the striatum in the MPTP group. Although DA tissue analysis revealed no significant increase in striatal DA or 3,4-Dihydroxyphenylacetic acid levels (DOPAC) in the MPTP group treated with GA, DA turnover (DOPAC/DA) recovered back to VEH levels following GA treatment. GA treatment effectively reversed clinical (motor dysfunction) and pathology (TH, IBA1, BDNF expression) of PD in a murine model.

Original languageEnglish
Pages (from-to)8-27
Number of pages20
JournalNeuroscience
Volume414
DOIs
StatePublished - 21 Aug 2019

Keywords

  • MPTP
  • Motor recovery
  • Parkinson's disease
  • glatiramer acetate
  • neuroinflammation
  • neurotrophic factors

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