Anterior cingulate cortical transplantation in transgenic Huntington's disease mice.
Huntington's disease (HD) is an autosomal dominant disorder involving progressive neurodegeneration of the corpus striatum and cerebral cortex. Transgenic mice, in which exon 1 of the human HD gene with an expanded trinucleotide repeat is expressed, develop a neurodegenerative syndrome that closely models human HD. Transplantation of wild-type donor cortex into the anterior cingulate cortex of neonatal HD mice (R6/1 line) was found to delay the onset of a specific motor deficit, rear-paw clasping. However, transplantation did not significantly enhance motor performance on a suspended horizontal rod, a behavioural measure of fine motor co-ordination. Control experiments in which the anterior cingulate cortex was resected, but no donor cortical tissue was transplanted, showed no behavioural benefit. In fact, wild-type littermate mice that also underwent this surgical resection, were found to develop motor deficits similar to those exhibited by non-resected HD mice. These results suggest that the anterior cingulate cortex is an important area of pathology in this HD model, and that therapeutic approaches to HD may need to target cortical, as well as striatal areas.
van Dellen
A
A
University Laboratory of Physiology, University of Oxford, Oxford, UK.
Deacon
R
R
York
D
D
Blakemore
C
C
Hannan
A J
AJ
D000818:Animals; D000831:Animals, Newborn; D016380:Brain Tissue Transplantation; D003342:Corpus Striatum / Q000473:pathology / Q000502:physiology; D005260:Female; D006179:Gyrus Cinguli / Q000473:pathology / Q000637:transplantation*; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000601:surgery*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009043:Motor Activity; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D010455:Peptides / Q000235:genetics; D010641:Phenotype; D019680:Trinucleotide Repeat Expansion
C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; C097188:polyglutamine