GABA CONTENT AND GLUTAMIC ACID DECARBOXYLASE ACTIVITY IN BRAIN OF HUNTINGTON'S CHOREA PATIENTS AND CONTROL SUBJECTS¹

Abstract

—GABA contents are significantly decreased in the caudate nucleus, putamen‐globus pallidus, substantia nigra, and occipital cortex in autopsied brain from Huntington's chorea patients, as compared to values in the same regions from control subjects who have died without neurological disease. Homocarnosine levels are lower in choreic than in control brain, but only in the putamen‐globus pallidus and the cerebellar cortex are the differences significant. Activity of the enzyme which synthesizes GABA, glutamic acid decarboxylase, is reduced in the brains of some choreic patients, but may be equally low in brain of control subjects, even though the latter exhibit normal brain GABA content. Low glutamic acid decarboxylase activity in autopsied human brain is not uniquely characteristic of Huntington's chorea. No evidence was found in this study for an inhibitor of glutamic acid decarboxylase in choreic brain, nor for the presence of an isoenzyme with decreased affinity for glutamate. GABA aminotransferase, the enzyme which degrades GABA, was equally active in control and choreic brain; therefore, increased activity of this enzyme cannot account for the low brain GABA levels in Huntington's chorea.

Gamma-aminobutyrate aminotransferase activity in brains of schizophrenic patients

“…With regard to the effect of postmortem delay in an unfrozen state, we found no significant influence (Table 2). Previous studies on mouse and monkey brains have, however, shown a slow decline over a period of 24-120 hours (Urquhart et al, 1975;Sherif et al, 1991). Furthermore, our present results on the stability of rat brain GABA-T activity indicated that there is a loss of approximately 20% of the activity immediately after death (Table 4).…”

“…Urquhart, 1975;Fariello and Ticku, 1983;Fibiger and Lloyd, 1984;Gale, 1989;Perry etal., 1989; see also Lloyd and Morselli, 1987 for a review). Roberts (1972) suggested that, in schizophrenia, there might be a deficiency in the activity of certain neurons that utilize GABA as an inhibitory neurotransmitter and this hypothesis of an imbalance between dopaminergic and GABA-ergic neuronal activity in schizophrenia was further developed by van Kammen (1977).…”

Elevated postmortem monoamine oxidase B activity in the caudate nucleus in hUntington's disease compared to schizophrenics and controls

“…Postmortem studies have indicated a loss of choline acetyltransferase (CAT) activity presumably associated with atrophy of cholinergic interneurons in the striatum, and a reduction in glutamic acid decarboxylase (GAD) (Bird and Iversen, 1974;Bird et al, 1973;McGeer and McGeer, 1976;Urquart et aL, 1975). These results together with the observation that dopamine antagonists improve the choreiform movements (Klausaus and Rubovits, 1972) suggest the presence of dopaminergic overactivity due to the loss of cholinergic and gabergic inhibition.…”

Brain GABA editing by localized in vivo1H magnetic resonance spectroscopy

“…2 Alterations in gaba-ergic pathways and GABA levels have been associated with several neurological disorders. [3][4][5][6][7] Accordingly, the in vivo assay of GABA has been a goal of much work on changes in neurotransmission in subjects, e.g. after pharmacological treatment.…”