RT Journal Article
SR Electronic
T1 Grafting Neural Precursor Cells Promotes Functional Recovery in an SCA1 Mouse Model
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 13126
OP 13135
DO 10.1523/JNEUROSCI.0647-09.2009
VO 29
IS 42
A1 Satyan Chintawar
A1 Raphael Hourez
A1 Ajay Ravella
A1 David Gall
A1 David Orduz
A1 Myriam Rai
A1 Don Patrick Bishop
A1 Stefano Geuna
A1 Serge N. Schiffmann
A1 Massimo Pandolfo
YR 2009
UL http://www.jneurosci.org/content/29/42/13126.abstract
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.