QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, October 21, 2009, 29(42):13126-13135; doi:10.1523/JNEUROSCI.0647-09.2009

This Article Full Text Full Text (PDF) Supplemental Material Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Chintawar, S. Articles by Pandolfo, M. PubMed PubMed Citation Articles by Chintawar, S. Articles by Pandolfo, M.

 Previous Article  |  Next Article 

Neurobiology of Disease
Grafting Neural Precursor Cells Promotes Functional Recovery in an SCA1 Mouse Model

Satyan Chintawar,¹ Raphael Hourez,^2 * Ajay Ravella,^1 * David Gall,² David Orduz,² Myriam Rai,¹ Don Patrick Bishop,² Stefano Geuna,³ Serge N. Schiffmann,² and Massimo Pandolfo¹

¹Laboratory of Experimental Neurology and ²Laboratory of Neurophysiology, Brussels Free University (ULB), 1070 Brussels, Belgium, and ³Department of Clinical and Biological Sciences and Cavalieri Ottolenghi Scientific Institute, University of Turin, Orbassano (TO), 10043 Italy

Correspondence should be addressed to Prof. Massimo Pandolfo, Laboratory of Experimental Neurology, Brussels Free University (ULB), Route de Lennik 808, 1070 Brussels, Belgium. Email: massimo.pandolfo{at}ulb.ac.be

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.

---

Received Feb. 7, 2009; accepted Sept. 1, 2009.

Correspondence should be addressed to Prof. Massimo Pandolfo, Laboratory of Experimental Neurology, Brussels Free University (ULB), Route de Lennik 808, 1070 Brussels, Belgium. Email: massimo.pandolfo{at}ulb.ac.be

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help