Behavioural brain research, 2011-03, Vol.217 (2), p.369-378
2011
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Mesenchymal stem cell transplantation and DMEM administration in a 3NP rat model of Huntington's disease: Morphological and behavioral outcomes
- Ist Teil von
- Behavioural brain research, 2011-03, Vol.217 (2), p.369-378
- Ort / Verlag
- Shannon: Elsevier B.V
- Erscheinungsjahr
- 2011
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- ▶ Intrastriatal Tp (200,000 MSCs) provided the most protection against 3NP deficits. ▶In vitro, MSCs have transcripts for BDNF, GDNF, CNTF, NGF and NT3. ▶In vivo, the absence of migration and no differentiation of the transplanted MSCs. ▶ Recovery due to the production of BDNF, collagen type-I and fibronectin by MSCs. ▶ Weaker recovery induced by DMEM as compared to MSCs does not involve such factors. 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0166-4328eISSN: 1872-7549DOI: 10.1016/j.bbr.2010.11.006Titel-ID: cdi_proquest_miscellaneous_860380764
- Format
- –
- Schlagworte
- 3NP intoxication, Adult and adolescent clinical studies, Animals, Behavior, Animal, Behavioral psychophysiology, Biological and medical sciences, Brain - metabolism, Cell Differentiation - drug effects, Cell Differentiation - physiology, Cells, Cultured, Convulsants - toxicity, Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases, Disease Models, Animal, DMEM, Dopamine and cAMP-Regulated Phosphoprotein 32 - genetics, Dopamine and cAMP-Regulated Phosphoprotein 32 - metabolism, Fundamental and applied biological sciences. Psychology, Gene Expression Regulation - drug effects, Hindlimb - drug effects, Hindlimb - physiopathology, Huntington Disease - chemically induced, Huntington Disease - pathology, Huntington Disease - physiopathology, Huntington Disease - surgery, Huntington's disease, Male, Medical sciences, Mesenchymal Stem Cell Transplantation - methods, Mesenchymal stem cells, Motor Activity - drug effects, Motor Activity - physiology, Nerve Growth Factors - genetics, Nerve Growth Factors - metabolism, Nervous system (semeiology, syndromes), Nervous system as a whole, Neurology, Nitro Compounds - toxicity, Organic mental disorders. Neuropsychology, Osteoblasts - drug effects, Osteoblasts - physiology, Phosphopyruvate Hydratase - genetics, Phosphopyruvate Hydratase - metabolism, Propionates - toxicity, Psychology. Psychoanalysis. Psychiatry, Psychology. Psychophysiology, Psychomotor Performance - physiology, Psychopathology. Psychiatry, Rats, Rats, Sprague-Dawley, RNA, Messenger - metabolism, Time Factors, Transplantation, Trophic factors