Tissue culture evidence for a circulating neurotoxin in Huntington's chorea.
We explored with tissue culture techniques the possibility that a circulating neurotoxin might cause the premature loss of certain populations of neurons that characterizes Huntington's chorea (HC). Explants of striatum from newborn rats were grown in culture media containing 30% by volume of serum from drug-free HC patients or from healthy control subjects. Glutamic acid decarboxylase (GAD), the enzyme which synthesizes gamma-aminobutyric acid (GABA), was later assayed in these explants as an indicator of the health of GABAergic striatal neurons. The sera of 7 of 8 HC patients decreased GAD activity markedly when present as 30% of the tissue culture medium. When present in lower concentration (15%), HC sera either decreased or increased GAD activity in explants. Deproteinization of sera with perchloric acid did not abolish these effects on GAD activity. A depressant effect on GAD activity was detected in the cerebrospinal fluid of 1 of 4 HC patients tested. These experiments suggest the presence of a circulating neurotoxin, possibly excitotoxic to GABAergic striatal interneurons, and probably a small molecule. Identification of this substance could lead to an effective preventive treatment for persons genetically at risk for HC.
D000293:Adolescent; D000328:Adult; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology; D046508:Culture Techniques; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006801:Humans; D006816:Huntington Disease / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009498:Neurotoxins / Q000097:blood* / Q000494:pharmacology; D051381:Rats
D009498:Neurotoxins; D005968:Glutamate Decarboxylase