Stress resilience is established during development and is regulated by complement factors
Amrutha Swaminathan,
Michael Gliksberg,
Savani Anbalagan,
Noa Wigoda,
Gil Levkowitz
Affiliations
Amrutha Swaminathan
Department of Molecular Cell Biology, Weizmann Institute of Science, P.O. Box 26, Rehovot 7610001, Israel; Department of Molecular Neuroscience, Weizmann Institute of Science, P.O. Box 26, Rehovot 7610001, Israel; Corresponding author
Michael Gliksberg
Department of Molecular Cell Biology, Weizmann Institute of Science, P.O. Box 26, Rehovot 7610001, Israel; Department of Molecular Neuroscience, Weizmann Institute of Science, P.O. Box 26, Rehovot 7610001, Israel
Savani Anbalagan
Department of Molecular Cell Biology, Weizmann Institute of Science, P.O. Box 26, Rehovot 7610001, Israel; Department of Molecular Neuroscience, Weizmann Institute of Science, P.O. Box 26, Rehovot 7610001, Israel
Noa Wigoda
Department of Life Science Core Facilities, Weizmann Institute of Science, P.O. Box 26, Rehovot, 7610001, Israel
Gil Levkowitz
Department of Molecular Cell Biology, Weizmann Institute of Science, P.O. Box 26, Rehovot 7610001, Israel; Department of Molecular Neuroscience, Weizmann Institute of Science, P.O. Box 26, Rehovot 7610001, Israel; Corresponding author
Summary: Individuals in a population respond differently to stressful situations. While resilient individuals recover efficiently, others are susceptible to the same stressors. However, it remains challenging to determine if resilience is established as a trait during development or acquired later in life. Using a behavioral paradigm in zebrafish larvae, we show that resilience is a stable and heritable trait, which is determined and exhibited early in life. Resilient larvae show unique stress-induced transcriptional response, and larvae with mutations in resilience-associated genes, such as neuropeptide Y and miR218, are less resilient. Transcriptome analysis shows that resilient larvae downregulate multiple factors of the innate immune complement cascade in response to stress. Perturbation of critical complement factors leads to an increase in resilience. We conclude that resilience is established as a stable trait early during development and that neuropeptides and the complement pathway play positive and negative roles in determining resilience, respectively.
