L-pyroglutamate: an alternate neurotoxin for a rodent model of Huntington's disease.
Intrastriatal injections of L-Pyroglutamate (L-PGA) in mice produced behavioral and neuropathological effects that resemble in part the kainate-injected rat striatal model of Huntington's Disease (HD). The behavioral responses induced after unilateral injections of L-PGA included circling, postural asymmetry of head and trunk and possible dyskinesias. The neuropil in the injected striatum contained dilated profiles, degenerating neurons and oligodendroglia, and numerous phagocytic microglial-like cells. A dose response relation existed. The size of the lesion (expressed as a percent volume of the striatum destroyed) ranged from 1 +/- 0.18% at 0.02 mumoles to 20.2 +/- 3.97% at 200 mumoles L-PGA (pH = 7.3). L-PGA is a weak neurotoxin when compared to kainic acid. Several factors raise interest in the possible role of L-PGA in HD, including the recently reported elevated plasma levels of L-PGA in some HD patients, and these considered in the discussion.
D000818:Animals; D001479:Basal Ganglia / Q000473:pathology; D001480:Basal Ganglia Diseases / Q000139:chemically induced / Q000473:pathology; D003342:Corpus Striatum / Q000187:drug effects; D004195:Disease Models, Animal; D006816:Huntington Disease / Q000139:chemically induced / Q000473:pathology; D007608:Kainic Acid; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D011760:Pyrrolidinones / Q000633:toxicity*; D011761:Pyrrolidonecarboxylic Acid / Q000633:toxicity*
D011760:Pyrrolidinones; D007608:Kainic Acid; D011761:Pyrrolidonecarboxylic Acid