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VPAC1 and VPAC2 Receptor Heterozygosity Confers Distinct Biological Properties to BV2 Microglial Cells
Xin Ying Rachel Song1, Margo Iris Jansen1, Rubina Marzagalli1
1Laboratory of Cellular and Molecular Neuroscience, School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW 2007, Australia.
Cells
|June 11, 2025
Summary
Vasoactive intestinal polypeptide receptors 1 and 2 (VPAC1 and VPAC2) on microglia have distinct roles in neuroinflammation. VPAC2 regulates survival and stress responses, while VPAC1 is key for adapting to inflammatory stimuli like LPS.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglial cells are crucial for central nervous system (CNS) homeostasis.
- Dysfunctional microglia are implicated in neurodegenerative diseases.
- Vasoactive intestinal polypeptide receptors (VPAC1, VPAC2) are expressed by microglia, but their roles are unclear.
Purpose of the Study:
- To elucidate the distinct functions of VPAC1 and VPAC2 receptors in microglial regulation.
- To investigate the impact of VPAC1 and VPAC2 on microglial phenotype, migration, survival, and stress responses.
Main Methods:
- CRISPR-Cas9 gene editing to create VPAC1+/- and VPAC2+/- BV2 microglial cell lines.
- Biological and molecular assays to assess cell phenotype, migration, survivability, and unfolded protein response (UPR).
- Stimulation with lipopolysaccharide (LPS) to mimic inflammatory conditions.
Main Results:
- Both VPAC1+/- and VPAC2+/- cells showed altered polarization and increased migration.
- VPAC1+/- cells had enhanced survival and baseline UPR activation, but impaired UPR and resilience under LPS.
- VPAC2+/- cells showed impaired baseline UPR but restored UPR and improved survival under LPS.
Conclusions:
- VPAC1 and VPAC2 receptors play distinct, complementary roles in BV2 microglia.
- VPAC2 is vital for basal survival, ER stress response, and polarization.
- VPAC1 is essential for adaptive responses to inflammatory stimuli, impacting microglial resilience.
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