Separation, isolation, and membrane lipid profiling of selectively vulnerable and resilient neurons
Year: 2026
Type: preprint
Abstract: Certain neurons are more susceptible to pathogenic stressors and degenerate, while others remain resilient in neurodegenerative diseases. However, the mechanisms underlying this cell-to-cell heterogeneity in neuronal vulnerability remain unclear, primarily due to challenges in isolating vulnerable and resilient neurons to characterize their properties. In this study, we report the development of a novel cell-labeling method utilizing two cell-impermeable dyes to identify vulnerable and resilient neurons in culture, which are subsequently separated and isolated via fluorescence-activated cell sorting (FACS). As a proof-of-concept of a mechanistic study, we conducted lipidomic analysis to determine whether the lipid composition of membranes differs between vulnerable and resilient neurons to oxidative stress. This simple but unique method sets the groundwork for investigating the molecular underpinnings of selective neuronal vulnerability, which could inform new diagnostic strategies and therapeutic targets for neurodegenerative diseases.
Institutions: Harvard University, Massachusetts General Hospital
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7221691878