Sox-2 Positive Neural Progenitors in the Primate Striatum Undergo Dynamic Changes after Dopamine Denervation

PLoS One. 2013 Jun 18;8(6):e66377. doi: 10.1371/journal.pone.0066377. Print 2013.

Abstract

The existence of endogenous neural progenitors in the nigrostriatal system could represent a powerful tool for restorative therapies in Parkinson's disease. Sox-2 is a transcription factor expressed in pluripotent and adult stem cells, including neural progenitors. In the adult brain Sox-2 is expressed in the neurogenic niches. There is also widespread expression of Sox-2 in other brain regions, although the neurogenic potential outside the niches is uncertain. Here, we analyzed the presence of Sox-2(+) cells in the adult primate (Macaca fascicularis) brain in naïve animals (N = 3) and in animals exposed to systemic administration of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine to render them parkinsonian (N = 8). Animals received bromodeoxyuridine (100 mg/kg once a day during five consecutive days) to label proliferating cells and their progeny. Using confocal and electron microscopy we analyzed the Sox-2(+) cell population in the nigrostriatal system and investigated changes in the number, proliferation and neurogenic potential of Sox-2(+) cells, in control conditions and at two time points after MPTP administration. We found Sox-2(+) cells with self-renewal capacity in both the striatum and the substantia nigra. Importantly, only in the striatum Sox-2(+) was expressed in some calretinin(+) neurons. MPTP administration led to an increase in the proliferation of striatal Sox-2(+) cells and to an acute, concomitant decrease in the percentage of Sox-2(+)/calretinin(+) neurons, which recovered by 18 months. Given their potential capacity to differentiate into neurons and their responsiveness to dopamine neurotoxic insults, striatal Sox-2(+) cells represent good candidates to harness endogenous repair mechanisms for regenerative approaches in Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Corpus Striatum / metabolism*
  • Denervation
  • Dopamine / metabolism*
  • Fluorescent Antibody Technique
  • Macaca fascicularis
  • Male
  • Neural Stem Cells / metabolism*
  • SOXB1 Transcription Factors / metabolism*
  • Substantia Nigra / metabolism

Substances

  • SOXB1 Transcription Factors
  • Dopamine

Grants and funding

This study was supported by funding from Foundation Kutxa Obra social to RSP for a collaborative network to advance translational stem cell research for neurodegenerative disorders (Inbiomed, CIMA, UV), PD research network and by the UTE-project/Foundation for Applied Medical Research (F.I.M.A.) to MRL. CO and I-CM were supported by a Torres Quevedo grant awarded by the Spanish Ministry of Science and Innovation, and by the European Social Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.