Research article summary (published 19 Oct 2009):

Grafting neural precursor cells promotes functional recovery in an SCA1 mouse model.

Full 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.

Author information

Author/s: Chintawar, Satyan (S); Hourez, Raphael (R); Ravella, Ajay (A); Gall, David (D); Orduz, David (D); Rai, Myriam (M); Bishop, Don Patrick (DP); Geuna, Stefano (S); Schiffmann, Serge N (SN); Pandolfo, Massimo (M);

Affiliation: Laboratory of Experimental Neurology and 2Laboratory of Neurophysiology, Brussels Free University (ULB), Brussels, Belgium.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci), published in United States. (Language: eng)

Reference: 2009-Oct; vol 29 (issue 42) : pp 13126-35

Dates: Created 2009/10/22; Completed 2009/11/06;

PMID: 19846700, status: MEDLINE (last retrieval date: 11/6/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adult Stem Cells - physiology; transplantation Analysis of Variance Animals Cell Movement - physiology Cerebral Ventricles - cytology Dendrites - pathology; physiology Disease Models, Animal Green Fluorescent Proteins - genetics Hand Strength - physiology Humans Membrane Potentials - genetics; physiology Mice Mice, Transgenic

Mice, Transgenic Microtubule-Associated Proteins - metabolism Motor Activity - genetics; physiology Mutation Nerve Tissue Proteins - genetics; metabolism Neurons - pathology; physiology Nuclear Proteins - genetics Patch-Clamp Techniques Peptides - genetics Recovery of Function - physiology Spinocerebellar Ataxias - genetics; pathology; physiopathology; surgery Stem Cell Transplantation - methods Time Factors

Associated Chemicals: MAP2 protein, human (0) ; Microtubule-Associated Proteins (0) ; Nerve Tissue Proteins (0) ; Nuclear Proteins (0) ; Peptides (0) ; ataxin-1 (0) ; Green Fluorescent Proteins (147336-22-9) ; polyglutamine (26700-71-0)

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