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Partial recovery of dopaminergic pathway after graft of adult mesenchymal stem cells in a rat model of Parkinson's disease.

Abstract

Cellular therapy with adult stem cells appears as an opportunity for treatment of Parkinson's disease. To validate this approach, we studied the effects of transplantation of rat adult bone-marrow mesenchymal stem cells in a rat model of Parkinson's disease. Animals were unilaterally lesioned in the striatum with 6-hydroxydopamine. Two weeks later, group I did not undergo grafting, group II underwent sham grafting, group III was intra-striatal grafted with cells cultured in an enriched medium and group IV was intra-striatal grafted with cells cultured in a standard medium. Rotational amphetamine-induced behavior was measured weekly until animals were killed 6 weeks later. One week after graft, the number of rotations/min was stably decreased by 50% in groups III and IV as compared with groups I and II. At 8 weeks post-lesion, the density of dopaminergic markers in the nerve terminals and cell bodies, i.e. immunoreactive tyrosine hydroxylase, membrane dopamine transporter and vesicular monoamine transporter-2 was significantly higher in group III as compared with group I. Moreover, using microdialysis studies, we observed that while the rate of pharmacologically induced release of dopamine was significantly reduced in lesioned versus intact striatum in no grafted rats, it was similar in both sides in animals transplanted with mesemchymal stem cells. These data demonstrate that graft of adult mesemchymal stem cells reduces behavioral effects induced by 6-hydroxydopamine lesion and partially restores the dopaminergic markers and vesicular striatal pool of dopamine. This cellular approach might be a restorative therapy in Parkinson's disease.

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  • Authors+Show Affiliations

    ,

    INSERM U930, Laboratory Biophysique médicale & pharmaceutique, UFR Pharmacie, 31 avenue Monge, Tours, France.

    , , , , , , , ,

    Source

    Neurochemistry international 52:7 2008 Jun pg 1332-42

    MeSH

    Animals
    Antimetabolites
    Behavior, Animal
    Bromodeoxyuridine
    Cells, Cultured
    DNA Primers
    Dopamine
    Dopamine Plasma Membrane Transport Proteins
    Immunohistochemistry
    Male
    Mesenchymal Stem Cell Transplantation
    Microdialysis
    Neostriatum
    Oxidopamine
    Parkinson Disease, Secondary
    RNA
    Rats
    Rats, Sprague-Dawley
    Receptors, Dopamine D1
    Receptors, Dopamine D2
    Reverse Transcriptase Polymerase Chain Reaction
    Signal Transduction
    Substantia Nigra
    Tyrosine 3-Monooxygenase
    Vesicular Monoamine Transport Proteins

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    18372079

    Citation

    Bouchez, Gaëlle, et al. "Partial Recovery of Dopaminergic Pathway After Graft of Adult Mesenchymal Stem Cells in a Rat Model of Parkinson's Disease." Neurochemistry International, vol. 52, no. 7, 2008, pp. 1332-42.
    Bouchez G, Sensebé L, Vourc'h P, et al. Partial recovery of dopaminergic pathway after graft of adult mesenchymal stem cells in a rat model of Parkinson's disease. Neurochem Int. 2008;52(7):1332-42.
    Bouchez, G., Sensebé, L., Vourc'h, P., Garreau, L., Bodard, S., Rico, A., ... Chalon, S. (2008). Partial recovery of dopaminergic pathway after graft of adult mesenchymal stem cells in a rat model of Parkinson's disease. Neurochemistry International, 52(7), pp. 1332-42. doi:10.1016/j.neuint.2008.02.003.
    Bouchez G, et al. Partial Recovery of Dopaminergic Pathway After Graft of Adult Mesenchymal Stem Cells in a Rat Model of Parkinson's Disease. Neurochem Int. 2008;52(7):1332-42. PubMed PMID: 18372079.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Partial recovery of dopaminergic pathway after graft of adult mesenchymal stem cells in a rat model of Parkinson's disease. AU - Bouchez,Gaëlle, AU - Sensebé,Luc, AU - Vourc'h,Patrick, AU - Garreau,Lucette, AU - Bodard,Sylvie, AU - Rico,Angélique, AU - Guilloteau,Denis, AU - Charbord,Pierre, AU - Besnard,Jean-Claude, AU - Chalon,Sylvie, Y1 - 2008/03/10/ PY - 2008/01/31/received PY - 2008/02/06/accepted PY - 2008/3/29/pubmed PY - 2008/8/9/medline PY - 2008/3/29/entrez SP - 1332 EP - 42 JF - Neurochemistry international JO - Neurochem. Int. VL - 52 IS - 7 N2 - Cellular therapy with adult stem cells appears as an opportunity for treatment of Parkinson's disease. To validate this approach, we studied the effects of transplantation of rat adult bone-marrow mesenchymal stem cells in a rat model of Parkinson's disease. Animals were unilaterally lesioned in the striatum with 6-hydroxydopamine. Two weeks later, group I did not undergo grafting, group II underwent sham grafting, group III was intra-striatal grafted with cells cultured in an enriched medium and group IV was intra-striatal grafted with cells cultured in a standard medium. Rotational amphetamine-induced behavior was measured weekly until animals were killed 6 weeks later. One week after graft, the number of rotations/min was stably decreased by 50% in groups III and IV as compared with groups I and II. At 8 weeks post-lesion, the density of dopaminergic markers in the nerve terminals and cell bodies, i.e. immunoreactive tyrosine hydroxylase, membrane dopamine transporter and vesicular monoamine transporter-2 was significantly higher in group III as compared with group I. Moreover, using microdialysis studies, we observed that while the rate of pharmacologically induced release of dopamine was significantly reduced in lesioned versus intact striatum in no grafted rats, it was similar in both sides in animals transplanted with mesemchymal stem cells. These data demonstrate that graft of adult mesemchymal stem cells reduces behavioral effects induced by 6-hydroxydopamine lesion and partially restores the dopaminergic markers and vesicular striatal pool of dopamine. This cellular approach might be a restorative therapy in Parkinson's disease. SN - 0197-0186 UR - https://www.unboundmedicine.com/medline/citation/18372079/Partial_recovery_of_dopaminergic_pathway_after_graft_of_adult_mesenchymal_stem_cells_in_a_rat_model_of_Parkinson's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-0186(08)00031-4 DB - PRIME DP - Unbound Medicine ER -