Investigating age-related effects of autophagy on neuroglial cells
Autophagy is the primary waste recycling pathway in all our cells that targets and degrades misfolded proteins, aggregates and damaged organelles. It is essential for cell survival, bioenergetics, immunity and inflammation. Waste recycling by autophagy plays a pivotal role in neurons and their supporting glial cells of the central nervous system (CNS).
Multiple lines of evidence indicate that CNS autophagy is impacted by age. Age-related neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and motor neuron disease (MND) all shows protein aggregate accumulation in neurons and glial cells of the CNS indicating autophagy abnormalities. Conversely, many regimes that promote longevity, such as fasting, elevate autophagy.
Before we can modulate autophagy pathway for therapeutic purposes, we need an understanding of cell-specific neurotypical autophagy. So far many studies have investigated neuronal autophagy, but glial autophagy remains under-explored.
Our work will involve conducting immunohistochemistry, confocal microscopy and image analysis using computer software to quantify autophagy flux in microglia and oligodendrocytes.
Aims
This project will analyse tissue from a novel transgenic autophagy reporter mouse model (RFP-EGFP-LC3) to quantify autophagy in vivo to study the effects of ageing on glial autophagy dynamics. Brain and lumbar spinal cord tissue have been already collected and cryosectioned from adult (6 months), middle-aged (12 months) and advanced aged (18 months) transgenic autophagy reporter mice.
The findings will reflect fundamental cell type-specific differences in autophagy pathway dynamics in the CNS and their responses to ageing to inform development of therapeutic strategies for age-related neurodegenerative diseases such as MND.
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