High-Throughput Analysis of Age-Dependent Protein Changes in Layer II/III of the Human Orbitofrontal Cortex
Year: 2016
Type: dissertation
Study design: Observational Study
Abstract: Studies on the orbitofrontal cortex (OFC) during normal aging have shown a decline in cognitive functions, a loss of spines/synapses in layer III and gene expression changes related to neural communication. Biological changes during the course of normal aging are summarized into 9 hallmarks based on aging in peripheral tissue. Whether these hallmarks apply to non-dividing brain tissue is not known. Therefore, we opted to perform large-scale proteomic profiling of the OFC layer II/III during normal aging from 15 young and 18 old male subjects. MaxQuant was utilized for label-free quantification and statistical analysis by the Random Intercept Model (RIM) identified 118 differentially expressed (DE) age-related proteins. Altered neural communication was the most represented hallmark of aging (54% of DE proteins), highlighting the importance of communication in the brain. Functional analysis showed enrichment in GABA/glutamate signaling and pro-inflammatory responses. The former may contribute to alterations in excitation/inhibition, leading to cognitive decline during aging.
Source: TSpace (University of Toronto)
Author: Fenika Kapadia
Language: English
Subfield: Aging
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2586385900