Showing papers by "Patrick L. McGeer published in 1971"

Distribution of tyrosine hydroxylase in human and animal brain.

Abstract: The activity of tyrosine hydroxylase (EC 1.10.3.1) when assayed under ideal conditions in young human brains, was comparable to that in brains of other species in level of activity and distribution. The highest levels of activity were in the putamen, caudate nucleus and substantia nigra, in keeping with data on other species. The caudate activity in human brain appeared to decrease substantially with increasing age. In both humans and baboons, the enzyme in the neostriatum was particle-bound and inhibited by the 2-amino-4-hydroxy-6,7-dimethyltetrahydropteridine cofactor system. In the substantia nigra it was soluble and stimulated by the 2-amino-4-hydroxy-6,7-dimethyltetrahydropteridine cofactor system. The data suggest that tyrosine hydroxylase may be produced in a soluble form in the cell bodies of the substantia nigra but become bound as it moves toward the nerve endings in the putamen and caudate nucleus. The bound form of the enzyme was unstable but the soluble form exhibited considerable stability.

Glutamic acid decarboxylase in Parkinson's disease and epilepsy

Abstract: THE ROLE of gamma aminobutyric acid (GABA) is not definitely established although its exclusive localization to the central nervous system in mammals has suggested that it has a key function in brain. The GABA shunt has long been considered an important source of cerebral oxidative metabolism.1 GABA itself has a depressant action on nerve transmission.2 Therefore, it may be a vital intermediate in an energy cycle or a neurotransmitter or both. The possibility that disturbances in GABA metabolism may be involved in certain human neurological disorders is suggested by two lines of evidence. First, GABA and its synthesizing enzyme, glutamic acid decarboxylase (GAD), are unequally distributed in brain. The high levels of GABA and GAD in extrapyramidal structuress-6 have drawn attention to the possibility that extrapyramidal disorders may be associated with deranged GABA metabolism. Second, the convulsant action of certain hydrazides which depress GAD activity has raised the question of whether some forms of epilepsy may involve faulty GABA metabolism.7 GAD is an enzyme which has a considerable degree of postmortem stability. Reasonably reliable results on GAD can therefore be obtained on human tissue. Reliable values for glutamic acid and GABA cannot be obtained as readily because the enzyme continues to function postmortem, converting the glutamic acid to GABA. This paper reports further details on the distribution of GAD in human brain. Normal and neurological cases are considered with particular reference to specific areas of the cortex and the basal ganglia. Data from coroner’s cases are compared with data from pa-

Cholinergic enzyme systems in Parkinson's disease.

Abstract: The levels of choline acetylase and cholinesterase in postmortem brain tissue were measured in Parkinson's disease cases, nonneurological illness cases, and accident victims. There was no significant difference between the parkinsonian and accident cases in any of the brain areas measured, although the younger accident victims had somewhat higher enzyme levels generally. Tyrosine hydroxylase was measurable in the basal ganglia of Parkinson's disease cases indicating the suggested impairment of brain catecholamine metabolism in this disease does not amount to a total block.