Chronically administered 3-nitropropionic acid produces selective lesions in the striatum and reduces muscle tonus.
Systemically administered 3-nitropropionic acid (3- NPA), irreversible inhibitor of succinate dehydrogenase, produced characteristic bilateral lesions in the striatum (STR) in the rat. Inside the lesion, neutrophils invaded and strong immunoreaction for IgG as well as complement factor C3b/C4b receptor (C3b/C4br) were observed. The core of the lesion lost the immunoreaction for glial fibrillary acidic protein (GFAP) while the marginal area had abundant GFAP-labeled astrocytes around the vessels. Intoxicated rats often became somnolent and were awkward in cooperative movement on a pole climbing test, but they had a quite good memory retention in a passive avoidance learning. Muscle tonus in some of the intoxicated rats became hypotonic with low voltage electromyogram (EMG) activity, especially in lower limbs. In summary, 3-NPA intoxicated rats had selective bilateral lesions in the STR and exhibited disturbances in a cooperative movement owing to the impairment in muscle tonus, thus it would be a useful animal model to deduce the central pathogenesis of Huntington's disease.
Shimano
Y
Y
Department of Physiology, Nagoya City University Medical School, Japan.
Kumazaki
M
M
Sakurai
T
T
Hida
H
H
Fujimoto
I
I
Fukuda
A
A
Nishino
H
H
D000818:Animals; D003179:Complement C3b / Q000032:analysis; D015935:Complement C4b / Q000032:analysis; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D004064:Digestive System / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006816:Huntington Disease; D007074:Immunoglobulin G / Q000032:analysis; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects*; D009574:Nitro Compounds; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D005904:Glial Fibrillary Acidic Protein; D007074:Immunoglobulin G; D009574:Nitro Compounds; D011422:Propionates; D003179:Complement C3b; D015935:Complement C4b; D013385:Succinate Dehydrogenase; C015392:3-nitropropionic acid