Morphological and biochemical changes in the aging brain: pathophysiological and possible therapeutic consequences

Area of Science:

• Neuroscience
• Aging Research
• Neurodegenerative Diseases

Background:

• Aging and SDAT are linked to reduced brain weight, fewer neurons, and increased astroglia.
• These changes correlate with diminished neurotransmitter synthesis and turnover, particularly affecting the dopaminergic (DAergic) system.

Purpose of the Study:

• To investigate the alterations in the dopaminergic system and related enzyme activities in aging brains and specific neurodegenerative diseases.
• To understand the implications of these neurochemical changes on neuronal function and associated pathologies.

Main Methods:

• Analysis of brain weight, neuronal counts, and astroglia in aging and SDAT brains.
• Assessment of Tyrosine Hydroxylase (TH) activity, dopamine (DA) concentration, and Monoamine Oxidase (MAO-A/B) activity.
• Evaluation of adenylate cyclase activity and D2 DA receptor density.

Main Results:

• Progressive loss of TH activity and DA concentration in the nigro-striatal system observed in SDAT and Parkinson disease.
• Inconsistent findings regarding MAO-B activity increase; MAO-B identified as a major biogenic amine degradative enzyme in human brain.
• Reduced DAergic parameters, including adenylate cyclase activity and D2 DA receptors, in aging and neurodegenerative conditions.

Conclusions:

• Dopaminergic system deficits are a significant feature of brain aging and neurodegenerative diseases like SDAT and Parkinson disease.
• Disturbances in neuronal feedback systems, including DAergic pathways, contribute to age-related pathophysiological and behavioral changes.