Neuroprotective properties of mildronate, a small molecule, in a rat model of parkinson's disease

Vija Z. Klusa, Sergejs Isajevs, Darja Svirina, Jolanta Pupure, Ulrika Beitnere, Juris Rumaks, Simons Svirskis, Baiba Jansone, Zane Dzirkale, Ruta Muceniece, Ivars Kalvinsh, Harry V. Vinters

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Previously, we have found that mildronate [3-(2,2,2-trimethylhydrazinium) propionate dihydrate], a small molecule with charged nitrogen and oxygen atoms, protects mitochondrial metabolism that is altered by inhibitors of complex I and has neuroprotective effects in an azidothymidine-neurotoxicity mouse model. In the present study, we investigated the effects of mildronate in a rat model of Parkinson's disease (PD) that was generated via a unilateral intrastriatal injection of the neurotoxin 6-hydroxydopamine (6-OHDA). We assessed the expression of cell biomarkers that are involved in signaling cascades and provide neural and glial integration: the neuronal marker TH (tyrosine hydroxylase); ubiquitin (a regulatory peptide involved in the ubiquitin-proteasome degradation system); Notch-3 (a marker of progenitor cells); IBA-1 (a marker of microglial cells); glial fibrillary acidic protein, GFAP (a marker of astrocytes); and inducible nitric oxide synthase, iNOS (a marker of inflammation). The data show that in the 6-OHDA-lesioned striatum, mildronate completely prevented the loss of TH, stimulated Notch-3 expression and decreased the expression of ubiquitin, GFAP and iNOS. These results provide evidence for the ability of mildronate to control the expression of an array of cellular proteins and, thus, impart multi-faceted homeostaticmechanisms in neurons and glial cells in a rat model of PD. We suggest that the use of mildronate provides a protective effect during the early stages of PD that can delay or halt the progression of this neurodegenerative disease.

Original languageEnglish
Pages (from-to)4465-4487
Number of pages23
JournalInternational Journal of Molecular Sciences
Volume11
Issue number11
DOIs
Publication statusPublished - Nov 2010
Externally publishedYes

Keywords*

  • 6-ohda model
  • Mildronate
  • Neuroimmunological biomarkers
  • Parkinson's disease
  • Small molecule

Field of Science*

  • 1.6 Biological sciences
  • 3.1 Basic medicine

Publication Type*

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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