RISK FACTOR FOR ALCOHOL'S NEUROPATHOLOGICAL EFFECTS

Project Details

Description

Arylsulfatase A (E.C. 3.1.6.1.) (ASA), an enzyme found in both human brain
and blood, catalyzes the degradation of sulfatides. Variant forms of this
enzyme, identified by discontinuous electrophoresis, have been shown to
occur with relatively high frequency in blood of alcoholic patients. The
hypothesis of this research proposal is that variant ASA's are inherited
risk factors for the neuropathological effects of alcohol. In order to investigate this proposal, blood samples will be obtained from
60 alcoholic, non-schizophrenic patients, 60 schizophrenic, non-alcoholic
patients, 10 patients with both alcoholism and schizophrenia, and 60 normal
controls. These blood samples will be analyzed by discontinuous
electrophoresis for variant ASA's. The variant and normal ASA's will be
characterized and compared by kinetic analysis with naturally occurring
sulfatides, by isoelectric focusing, and by a study of physical stability
under a variety of conditions (e.g., heat denaturation). If in vivo activity of variant ASA's is deficient, an accumulation of
sulfatides, the substrate of ASA, would be expected to occur in urine.
Therefore, urinary sulfatide levels will be measured in all subjects. To
investigate the possibility that variant ASA's may be under genetic
control, the electrophoretic properties of the enzyme taken from first and
second degree relatives of subjects with variant ASA's will be studied. Selected alcoholic patients will be investigated using intelligence and
neuropsychological testing as well as neurophysiological testing. The
neurophysiological parameters that will be measured include
electromyography, nerve conduction, including F response and H reflex, and
cerebral evoked responses (brainstem auditory, pattern reversal visual, and
somatosensory cerebral and subcortical evoked responses). Two subgroups of
alcoholic patients will be studied, one with variant ASA's and one with
normal enzyme who have been matched for age, sex, and chronicity and
severity of alcoholism. If the hypothesis regarding variant ASA's and chronic alcohol intake is
correct, this would explain the neuropathological course of the disease in
some alcoholic patients. Moreover, it would allow identification of normal
subjects who would be at risk to the neuropathological effects of alcohol.
StatusFinished
Effective start/end date9/28/845/31/88

Funding

  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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