PT  - JOURNAL ARTICLE
AU  - Satyan Chintawar
AU  - Raphael Hourez
AU  - Ajay Ravella
AU  - David Gall
AU  - David Orduz
AU  - Myriam Rai
AU  - Don Patrick Bishop
AU  - Stefano Geuna
AU  - Serge N. Schiffmann
AU  - Massimo Pandolfo
TI  - Grafting Neural Precursor Cells Promotes Functional Recovery in an SCA1 Mouse Model
AID  - 10.1523/JNEUROSCI.0647-09.2009
DP  - 2009 Oct 21
TA  - The Journal of Neuroscience
PG  - 13126--13135
VI  - 29
IP  - 42
4099  - http://www.jneurosci.org/content/29/42/13126.short
4100  - http://www.jneurosci.org/content/29/42/13126.full
SO  - J. Neurosci.2009 Oct 21; 29
AB  - 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.