Striatal and cortical neurochemical changes induced by chronic metabolic compromise in the 3-nitropropionic model of Huntington's disease.
In the present study, we aimed to determine the time-course of neurochemical changes occurring following metabolic impairments produced by 3-nitropropionic (3NP) acid in a rat model of Huntington's disease. We found that the occurrence of striatal lesions was accompanied by (1) strong transcriptional alterations within the degenerative lateral striatum, (2) receptor upregulations within the preserved medial striatum, and (3) transcriptional increases within the unaltered cerebral cortex. These phenomena were preceded by transcriptional modifications in striatal subareas prone to degeneration even before the lesion was visible but not in the overlying cortex, known to be spared in this model. Of great interest, the density of A(2A) receptor binding sites, located on striato-pallidal neurons, was (1) downregulated at the time of worsening of symptoms and (2) strongly upregulated within the spared medial striatum after the lesion occurrence. This study therefore highlights the differential neurochemical responses produced by 3NP depending on the fate of the metabolically inhibited area and strongly suggests the involvement of A(2A) receptors in the development of striatal pathology under metabolic compromise.
Blum
David
D
Laboratoire de Neurophysiologie, ULB-Erasme, CP601, 808 Route de Lennik, 1070 Brussels, Belgium. David.Blum@ulb.ac.be
Galas
Marie-Christine
MC
Gall
David
D
Cuvelier
Laetitia
L
Schiffmann
Serge N
SN
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002908:Chronic Disease; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D006816:Huntington Disease / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D007279:Injections, Subcutaneous; D008297:Male; D009574:Nitro Compounds; D011422:Propionates / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew
D009574:Nitro Compounds; D011422:Propionates; D012333:RNA, Messenger; C015392:3-nitropropionic acid