N-Acetylaspartate and DARPP-32 levels decrease in the corpus striatum of Huntington's disease mice.
Huntington's disease (HD) is an autosomal dominant condition involving progressive neurodegeneration, primarily the corpus striatum and cerebral cortex. We have used in vivo magnetic resonance spectroscopy (MRS) to assess specific neuronal markers in transgenic mice (R6/1 line) expressing exon I of the human huntingtin gene with an expanded CAG repeat. Levels of N-acetylaspartate (NAA), an indicator of healthy neuronal function, were significantly reduced (26%) in the corpus striatum of HD mice relative to wild-type littermates at 5 months of age. However, levels of cholines and creatine-phosphocreatine were not altered in the HD mice. Expression of dopamine- and cAMP-regulated phosphoprotein, 32 kDa (DARPP-32), was assessed by immunohistochemistry in the striatum of HD mice and found to be downregulated by 5 months and, even more dramatically, at 11 months of age. In contrast, expression of calbindin was not significantly decreased in HD mice. Our results suggest that the observed decreases in DARPP-32 and NAA may contribute to aberrant receptor signalling and neuronal dysfunction in HD.
van Dellen
A
A
University Laboratory of Physiology, University of Oxford.
Welch
J
J
Dixon
R M
RM
Cordery
P
P
York
D
D
Styles
P
P
Blakemore
C
C
Hannan
A J
AJ
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism*; D015415:Biomarkers; D064026:Calbindins; D002794:Choline / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology; D003401:Creatine / Q000378:metabolism; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010750:Phosphoproteins / Q000378:metabolism*; D064030:S100 Calcium Binding Protein G / Q000378:metabolism
D015415:Biomarkers; D064026:Calbindins; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D064030:S100 Calcium Binding Protein G; D001224:Aspartic Acid; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline