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Increased dopamine peroxidation in postmortem Parkinsonian brain
Angela De Iuliis1, Alessandro P Burlina, Roberta Boschetto
1Department of Diagnostics, University of Padua, Viale G. Colombo 3, Italy. angela.deiuliis@unipd.it
Abstract:
We have previously reported the presence, in human midbrain, of an enzymatic activity which catalyzes the formation of dopaminochrome from dopamine (DA) and hydrogen peroxide. Here, we report, for the first time, an increased DA peroxidizing activity in the midbrain and basal ganglia of autoptic Parkinsonian brains. The crude activity was determined spectrophotometrically in extracts of paraffin-embedded slices obtained from autopsied brain. No addition of substrate was necessary since endogenous substrates such as DA and hydrogen peroxide were present in the samples. In Parkinson's patients' midbrain, this activity was substantially increased compared to normal midbrain. Moreover, the DA peroxidizing activity, which was absent in basal ganglia of normal people, was detectable in all our Parkinson's patients. These observations suggest that a peroxidizing pathway of DA may be present in human brain. The increased peroxidizing activity in Parkinson's patients generates the toxic compound dopaminochrome which may play a role in the pathogenesis of this disease.
Insights
Researchers found increased dopamine (DA) peroxidizing activity in Parkinsonian brains, leading to toxic dopaminochrome formation. This suggests a novel pathway contributing to Parkinson
Area of Science:
- Neuroscience
- Biochemistry
- Pathology
Background:
- Previously identified enzymatic activity in human midbrain catalyzes dopaminochrome formation from dopamine (DA) and hydrogen peroxide.
- Dopaminochrome is a toxic compound implicated in neurodegenerative processes.
Purpose of the Study:
- To investigate dopamine (DA) peroxidizing activity in autoptic Parkinsonian brains.
- To determine if this activity differs between Parkinsonian and normal brain tissues.
Main Methods:
- Spectrophotometric determination of crude enzymatic activity in extracts of paraffin-embedded brain slices.
- Analysis of endogenous dopamine (DA) and hydrogen peroxide substrates within brain samples.
Main Results:
- Significantly increased DA peroxidizing activity observed in the midbrain of Parkinson's patients compared to controls.
- DA peroxidizing activity, absent in normal basal ganglia, was detected in all Parkinsonian patients' basal ganglia.
Conclusions:
- A DA peroxidizing pathway is suggested to be present in the human brain.
- Elevated DA peroxidizing activity in Parkinson's patients generates toxic dopaminochrome, potentially contributing to disease pathogenesis.