Neurotransmitter-related enzymes and indices of hypoxia in senile dementia and other abiotrophies.
Author(s): Bowen DM, Smith CB, White P, Davison AN
Publication: Brain, 1976, Vol. 99, Page 459-96
PubMed ID: 11871 PubMed Review Paper? No
Purpose of Paper
Conclusion of Paper
Studies
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Study Purpose
The purpose of this study was to examine the effects of simulated warm ischemia time (by incubation in a 37 degree C water bath for 0, 6 or 18 h) on GAD activity and the abundance of neuronin type proteins S-5 and S-6 in cortical biopsy specimens.
Summary of Findings:
Incubation of specimens at 37 degrees C resulted in a 24% reduction in GAD activity over the first 6 h. S-6 also decreased 14% over the first 6 hours, but no decrease was noted in S-5. From 6-18 h no further changes in S-5 or S-6 abundance were noted and GAD activity was not assayed. The authors conclude that GAD activity is rather unstable during ischemia, but concentrations of S-5 and S-6 are stable for up to 18 h of warm ischemia.
Biospecimens
Preservative Types
- None (Fresh)
Diagnoses:
- Normal
Platform:
Analyte Technology Platform Protein Enzyme assay Protein Spectrophotometry Pre-analytical Factors:
Classification Pre-analytical Factor Value(s) Preaquisition Warm ischemia time 0 h
18 h
6 h
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Study Purpose
The purpose of this study was to investigate the differential effects of cold ischemia on activity of GAD, AAD, and CAT in caudate nucleus. Frontal cortex and caudate nucleus were removed from a postmortem brain within 1.5 h of death and incubated for 27 h at room temperature or in a 37 degree C water bath that cooled to room temperature at a rate of 1 degree C per hour, mimicking the rate of heat dissipation postmortem.
Summary of Findings:
Specimens from the frontal cortex and caudate nucleus of 1 patient were cooled by 1 degree C/h until room temperature was reached or incubated at room temperature for 27 h after which GAD, AAD and CAT activities were assayed. GAD activity remained at or above 80% that of control levels independent of controlled or spontaneous cooling methods or brain region. CAT activity in the caudate nucleus decreased to 76% of initial levels after room temperature incubation and to 67% of initial levels when the specimen was cooled slowly. AAD in caudate nucleus decreased to 60% of initial level after room temperature and 48% when cooled slowly. The authors conclude that activity of AAD and CAT are highly dependent on post-mortem interval and speed at which the specimen is cooled.
Biospecimens
Preservative Types
- None (Fresh)
Diagnoses:
- Depression
- Autopsy
- Cardiovascular Disease
- Other diagnoses
Platform:
Analyte Technology Platform Protein Enzyme assay Pre-analytical Factors:
Classification Pre-analytical Factor Value(s) Biospecimen Acquisition Cold ischemia time Progressive decline to room temperature (1 degree C per h)
27 h at room temperature
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Study Purpose
The purpose of this study was to investigate the effects of age on brain and lung weight, the enzymatic activities of AAD, GAD, CAT, GGT, and on the concentrations of S-5, S-6 and total protein. Of note, specimens analyzed were subjected to a postmortem interval (PMI) of 7-31 h and corpse refrigeration prior to excision and incubation.
Summary of Findings:
Increasing age caused an a decrease in the caudate nucleus and an increase in temporal lobe weight, which were particularly evident in the senile dementia group that consisted of older individuals (79-97 y versus 50-100 y for control). No significant effects of patient age were found on any of the biochemical parameters examined; however trends toward decreasing GAD and AAD activity and increasing S-5 concentrations in the caudate nucleus, and decreasing S-6 concentrations with age in the cortex were observed. While GAD activity in the cortex and caudate nucleus were not altered by PMI, AAD activity was reduced by 74% after a PMI of 31 h compared to 7 h among normal cases but not cases of senile dementia.
Biospecimens
Preservative Types
- None (Fresh)
Diagnoses:
- Pneumonia/Respiratory Infection
- Cardiovascular Disease
- Autopsy
- Normal
- Other diagnoses
Platform:
Analyte Technology Platform Protein Enzyme assay Pre-analytical Factors:
Classification Pre-analytical Factor Value(s) Preaquisition Patient age 79-97 years
50-100 years
Biospecimen Acquisition Organ measurements Lung weight/body weight
Brain weight/body weight
Biospecimen Acquisition Biospecimen location Brain
Lung
Preaquisition Postmortem interval 7 h
15 h
19 h
24 h
31 h
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Study Purpose
The purpose of this study was to investigate the effects of oxygen deprivation and patient diagnosis (senile dementia, bronchopneumonia, pulmonary embolism, ventricular failure, congophilic angiopathy, Huntington's chorea, Parkinson's disease, and motor neuron disease) on brain and lung weight and the activities of AAD, GAD, CAT, GTP and S-5 and S-6 concentration in specimens from the caudate nucleus and cortex. Of note, specimens analyzed were subjected to a postmortem interval of 24 h or less and corpse refrigeration prior to excision and incubation.
Summary of Findings:
Increased lung weight as a percentage of body weight (2.4% versus 1.2%) was observed in patients with senile dementia versus normal controls. The authors note this may be because a large number of the senile dementia patients died from bronchopneumonia whereas the normal control group most often died from circulatory failure. No differences in total brain weight were observed between the groups. Pulmonary or circulatory defects including bronchopneumonia but not pulmonary embolism that are associated with oxygen deprivation led to a decrease in S-6 (20-21% of normal) concentrations and a decrease in AAD (8-19% of normal) and GAD activities (28-47% of normal) in the caudate. Decreased S-6 levels were a particularly good indicator of hypoxia and were predominantly reduced in the sulci versus gyri regions of the cortex. In the cortex, GAD decreased with oxygen deprivation to 53% of normal levels, but all other markers were unaffected. Neurologic disease altered GAD, AAD and CAT activities and S-6 levels, but no change in total protein concentration was observed. The authors conclude the GAD, AAD and CAT activities and the concentrations of S-6 in the cortex and caudate are indicators of oxygenation state and disease dependent differences are observed.
Biospecimens
Preservative Types
- None (Fresh)
Diagnoses:
- Other diagnoses
- Pneumonia/Respiratory Infection
- Cardiovascular Disease
- Huntington's Disease
- Parkinson's Disease
Platform:
Analyte Technology Platform Protein Enzyme assay Protein Lowry protein assay Protein Spectrophotometry Pre-analytical Factors:
Classification Pre-analytical Factor Value(s) Preaquisition Cause of death Bronchopulmonary Pneumonia
Cardiovascular failure
Pulmonary embolism
Preaquisition Prior patient medical condition Senile
Normal
Biospecimen Acquisition Organ measurements Lung/body weight
Brain/body weight
Biospecimen Acquisition Biospecimen location Lung
Brain
Preaquisition Postmortem interval 5-36 h