| Title | Grafting neural precursor cells promotes functional recovery in an SCA1 mouse model. | | Author(s) | Chintawar S, Hourez R, Ravella A, Gall D, Orduz D, Rai M, Bishop DP, Geuna S, Schiffmann SN, Pandolfo M | | Institution | Laboratory of Experimental Neurology and 2Laboratory of Neurophysiology, Brussels Free University (ULB), Brussels, Belgium. | | Source | J Neurosci 2009 Oct 21; 29(42):13126-35. | | MeSH | Adult Stem Cells
Analysis of Variance
Animals
Cell Movement
Cerebral Ventricles
Dendrites
Disease Models, Animal
Green Fluorescent Proteins
Hand Strength
Humans
Membrane Potentials
Mice
Mice, Transgenic
Microtubule-Associated Proteins
Motor Activity
Mutation
Nerve Tissue Proteins
Neurons
Nuclear Proteins
Patch-Clamp Techniques
Peptides
Recovery of Function
Spinocerebellar Ataxias
Stem Cell Transplantation
Time Factors
| | Abstract | The B05 transgenic SCA1 mice, expressing human ataxin-1 with an expanded polyglutamine tract in cerebellar Purkinje cells (PCs), recapitulate many pathological and behavioral characteristics of the neurodegenerative disease spinocerebellar ataxia type 1 (SCA1), including progressive ataxia and PC loss. We transplanted neural precursor cells (NPCs) derived from the subventricular zone of GFP-expressing adult mice into the cerebellar white matter of SCA1 mice when they showed absent (5 weeks), initial (13 weeks), and significant (24 weeks) PC loss. Only in mice with significant cell loss, grafted NPCs migrated into the cerebellar cortex. These animals showed improved motor skills compared with sham-treated controls. No grafted cell adopted the morphological and immunohistochemical characteristics of PCs, but the cerebellar cortex in NPC-grafted SCA1 mice had a significantly thicker molecular layer and more surviving PCs. Perforated patch-clamp recordings revealed a normalization of the PC basal membrane potential, which was abnormally depolarized in sham-treated animals. No significant increase in levels of several neurotrophic factors was observed, suggesting, along with morphological observation, that the neuroprotective effect of grafted NPCs was mediated by direct contact with the host PCs. We postulate that a similar neuroprotective effect of NPCs may be applicable to other cerebellar degenerative diseases. | | Language | eng | | Pub Type(s) | Journal Article
Research Support, Non-U.S. Gov't
| | PubMed ID | 19846700 |
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