Neurochemical-clinical correlates in Huntington's disease--applications of brain banking techniques.
Our present understanding of the neuronal abnormalities of Huntington's disease (HD) owes everything to the post mortem study of brain tissue from patients with this disorder. HD was one of the first brain disorders to be studied after systematic brain banking, and it is now well defined in terms of its histological and neurotransmitter pathology. Having established the neurotransmitter systems that are particularly affected in HD (and which include striatal and pallidal GABAergic pathways), it has proven possible to assess post-mortem neurochemistry in the light of pre-mortem clinical information to identify some of the neurotransmitter correlates of the individual motor, behavioural and cognitive symptoms seen in the disease. Thus a further loss of pallidal GABA is associated with a diminution of chorea in HD, while the dementia that occurs in the great majority of cases is related to amino acid transmitter losses in the caudate, but not the cortex. The neurochemical pattern of neuronal loss in the brain in HD has also indicated the possible mechanism for the pathogenesis of the disease: excitotoxic damage via the glutamate/NMDA receptor. Banked brain tissue has also provided the means for the search for abnormal concentrations of biochemical toxins that might bring about this damage. One such endogenous neurotoxin, the tryptophan metabolite quinolinic acid, was found to be unchanged in HD, although another little-studied, but toxic, tryptophan metabolite, 3-hydroxykynurenine, was found to be increased in HD brain samples.(ABSTRACT TRUNCATED AT 250 WORDS)
Reynolds
G P
GP
Department of Biomedical Science, University of Sheffield, United Kingdom.
Pearson
S J
SJ
D001923:Brain Chemistry / Q000502:physiology*; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D018377:Neurotransmitter Agents / Q000378:metabolism; D014015:Tissue Banks; D014364:Tryptophan / Q000378:metabolism
D018377:Neurotransmitter Agents; D014364:Tryptophan