Differential expression of synaptic and interneuron genes in the aging human prefrontal cortex
Adith Mohan1, Anbupalam Thalamuthu2, Karen A Mather2
1Centre for Healthy Brain Ageing (CHeBA), University of New South Wales (UNSW) Australia, Sydney, New South Wales, Australia; School of Psychiatry, UNSW Australia, Sydney, New South Wales, Australia; Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, New South Wales, Australia.
Neurobiology of Aging
|July 22, 2018
Summary
Brain aging alters gene expression in the prefrontal cortex, particularly for interneuron and synaptic proteins. These changes correlate with brain volume, suggesting a role in cognitive decline.
Area of Science:
- Neuroscience
- Genetics
- Aging Research
Background:
- Altered inhibition-excitation balance is a hallmark of brain aging.
- Synaptic and interneuron function are critical for prefrontal cortex (PFC) network dynamics.
Purpose of the Study:
- To investigate age-related changes in the expression of genes encoding synaptic and interneuron proteins in the human PFC.
- To determine correlations between these gene expression changes and human brain volumes across the lifespan.
Main Methods:
- Analysis of postmortem PFC tissue from 37 individuals (aged 18-78 years).
- Quantitative assessment of 14 genes related to synapses and interneurons.
- Correlation analysis with brain volumes and glial markers (GFAP, IBA1).
Main Results:
- The majority of examined genes showed age-related expression changes, predominantly downregulation.
- Expression of calbindin, somatostatin, and cholecystokinin (interneuron markers) decreased with age.
- PSD95, GAP43, and VGLUT1 (synaptic markers) exhibited significant age-related expression changes.
- Calbindin, somatostatin, cholecystokinin, and GAP43 remained significant after controlling for glial markers.
- Calbindin and complexin 2 expression correlated with total brain volume.
- Synaptophysin expression correlated with cortical gray matter volume.
Conclusions:
- Age-related changes in genes maintaining inhibition-excitation balance and regulating PFC network dynamics are evident.
- These molecular alterations may contribute to the neurobiological changes observed during brain aging.
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