Reduced activity of cortico-striatal fibres in the R6/2 mouse model of Huntington's disease.
We have used the R6/2 mice to study cortico-striatal glutamatergic transmission by microdialysis in freely moving mice. Basal extracellular striatal glutamate concentrations were lower in R6/2 mice at 12 weeks of age, but not at 6 weeks of age, when neurological symptoms start to develop. In contrast, K-induced glutamate release was blunted in the striatum of R6/2 mice at both 6 and 12 weeks of age as compared with age-matched controls. We also found a substantial reduction in striatal pro-BDNF (brain derived neurotrophic factor) levels associated with no changes in the mature form of BDNF, as assessed by immunoblotting, in 12-week-old R6/2 mice, suggesting a reduced turnover rate of BDNF in the striatum of these mice. These data support the hypothesis of a cortico-striatal dysfunction in Huntington's disease.
Traficante
Anna
A
Department of Neuroscience, Istituto Neurologico Mediterraneo Neuromed, Località Camerelle, Pozzilli, Italy.
Riozzi
Barbara
B
Cannella
Milena
M
Rampello
Liborio
L
Squitieri
Ferdinando
F
Battaglia
Giuseppe
G
D000375:Aging / Q000235:genetics / Q000378:metabolism; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism* / Q000503:physiopathology; D003342:Corpus Striatum / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology; D045604:Extracellular Fluid / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017551:Microdialysis; D009434:Neural Pathways / Q000378:metabolism* / Q000503:physiopathology; D009435:Synaptic Transmission / Q000235:genetics
D019208:Brain-Derived Neurotrophic Factor; D018698:Glutamic Acid