Mesenchymal stem cell transplantation and DMEM administration in a 3NP rat model of Huntington's disease

Morphological and behavioral outcomes

Julien Rossignol, Cécile Boyer, Xavier Lévèque, Kyle Fink, Reynald Thinard, Frédéric Blanchard, Gary L. Dunbar, Laurent Lescaudron

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Transplantation of mesenchymal stem cells (MSCs) may offer a viable treatment for Huntington's disease (HD). We tested the efficacy of MSC transplants to reduce deficits in a 3-nitropropionic acid (3NP) rat model of HD. Five groups of rats (Sham, 3NP, 3NP+vehicle, 3NP+TPlow, 3NP+TPhigh), were given PBS or 3NP intraperitoneally, twice daily for 42 days. On day 28, rats in all groups except Sham and 3NP, received intrastriatal injections of either 200,000 MSCs (TPlow), 400,000 (TPhigh) MSCs or DMEM (VH, the vehicle for transplantation). MSCs survived 72 days without inducing a strong inflammatory response from the striatum. Behavioral sparing was observed on tests of supported-hindlimb-retraction, unsupported-hindlimb-retraction, visual paw placement and stepping ability for 3NP+TPlow rats and on the unsupported-hindlimb-retraction and rotarod tasks for 3NP+VH rats. Relative to 3NP controls, all treated groups were protected from 3NP-induced enlargement of the lateral ventricles. In vitro, MSCs expressed transcripts for numerous neurotrophic factors. In vivo, increased striatal labeling in BDNF, collagen type-I and fibronectin (but not GDNF or CNTF) was observed in the brains of MSC-transplanted rats but not in DMEM-treated rats. In addition, none of the transplanted MSCs expressed neural phenotypes. These findings suggest that factors other than neuronal replacement underlie the behavioral sparing observed in 3NP rats after MSC transplantation.

Original languageEnglish (US)
Pages (from-to)369-378
Number of pages10
JournalBehavioural Brain Research
Volume217
Issue number2
DOIs
StatePublished - Mar 1 2011
Externally publishedYes

Fingerprint

Mesenchymal Stem Cell Transplantation
Huntington Disease
Mesenchymal Stromal Cells
Hindlimb
3-nitropropionic acid
Ciliary Neurotrophic Factor
Glial Cell Line-Derived Neurotrophic Factor
Corpus Striatum
Aptitude
Lateral Ventricles
Brain-Derived Neurotrophic Factor
Nerve Growth Factors
Collagen Type I
Fibronectins
Brain Stem

Keywords

  • 3NP intoxication
  • DMEM
  • Huntington's disease
  • Mesenchymal stem cells
  • Transplantation
  • Trophic factors

ASJC Scopus subject areas

  • Behavioral Neuroscience

Cite this

Mesenchymal stem cell transplantation and DMEM administration in a 3NP rat model of Huntington's disease : Morphological and behavioral outcomes. / Rossignol, Julien; Boyer, Cécile; Lévèque, Xavier; Fink, Kyle; Thinard, Reynald; Blanchard, Frédéric; Dunbar, Gary L.; Lescaudron, Laurent.

In: Behavioural Brain Research, Vol. 217, No. 2, 01.03.2011, p. 369-378.

Research output: Contribution to journalArticle

Rossignol, Julien ; Boyer, Cécile ; Lévèque, Xavier ; Fink, Kyle ; Thinard, Reynald ; Blanchard, Frédéric ; Dunbar, Gary L. ; Lescaudron, Laurent. / Mesenchymal stem cell transplantation and DMEM administration in a 3NP rat model of Huntington's disease : Morphological and behavioral outcomes. In: Behavioural Brain Research. 2011 ; Vol. 217, No. 2. pp. 369-378.
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