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Mesenchymal stem cell transplantation and DMEM administration in a 3NP rat model of Huntington's disease: morphological and behavioral outcomes.
Behav Brain Res. 2011 Mar 01; 217(2):369-78.BB

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+TP(low), 3NP+TP(high)), 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 (TP(low)), 400,000 (TP(high)) 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+TP(low) 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.

Authors+Show Affiliations

INSERM U643, Nantes F44093, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21070819

Citation

Rossignol, Julien, et al. "Mesenchymal Stem Cell Transplantation and DMEM Administration in a 3NP Rat Model of Huntington's Disease: Morphological and Behavioral Outcomes." Behavioural Brain Research, vol. 217, no. 2, 2011, pp. 369-78.
Rossignol J, Boyer C, Lévèque X, et al. Mesenchymal stem cell transplantation and DMEM administration in a 3NP rat model of Huntington's disease: morphological and behavioral outcomes. Behav Brain Res. 2011;217(2):369-78.
Rossignol, J., Boyer, C., Lévèque, X., Fink, K. D., Thinard, R., Blanchard, F., Dunbar, G. L., & Lescaudron, L. (2011). Mesenchymal stem cell transplantation and DMEM administration in a 3NP rat model of Huntington's disease: morphological and behavioral outcomes. Behavioural Brain Research, 217(2), 369-78. https://doi.org/10.1016/j.bbr.2010.11.006
Rossignol J, et al. Mesenchymal Stem Cell Transplantation and DMEM Administration in a 3NP Rat Model of Huntington's Disease: Morphological and Behavioral Outcomes. Behav Brain Res. 2011 Mar 1;217(2):369-78. PubMed PMID: 21070819.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mesenchymal stem cell transplantation and DMEM administration in a 3NP rat model of Huntington's disease: morphological and behavioral outcomes. AU - Rossignol,Julien, AU - Boyer,Cécile, AU - Lévèque,Xavier, AU - Fink,Kyle D, AU - Thinard,Reynald, AU - Blanchard,Frédéric, AU - Dunbar,Gary L, AU - Lescaudron,Laurent, Y1 - 2010/11/09/ PY - 2010/08/09/received PY - 2010/10/27/revised PY - 2010/11/01/accepted PY - 2010/11/13/entrez PY - 2010/11/13/pubmed PY - 2011/4/19/medline SP - 369 EP - 78 JF - Behavioural brain research JO - Behav Brain Res VL - 217 IS - 2 N2 - 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+TP(low), 3NP+TP(high)), 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 (TP(low)), 400,000 (TP(high)) 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+TP(low) 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. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/21070819/Mesenchymal_stem_cell_transplantation_and_DMEM_administration_in_a_3NP_rat_model_of_Huntington's_disease:_morphological_and_behavioral_outcomes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-4328(10)00730-8 DB - PRIME DP - Unbound Medicine ER -