Measuring Nonapoptotic Caspase Activity with a Transgenic Reporter in Mice.

Journal Article (Journal Article)

The protease caspase-3 is a key mediator of apoptotic programmed cell death. But weak or transient caspase activity can contribute to neuronal differentiation, axonal pathfinding, and synaptic long-term depression. Despite the importance of sublethal, or nonapoptotic, caspase activity in neurodevelopment and neural plasticity, there has been no simple method for mapping and quantifying nonapoptotic caspase activity (NACA) in rodent brains. We therefore generated a transgenic mouse expressing a highly sensitive and specific fluorescent reporter of caspase activity, with peak signal localized to the nucleus. As a proof of concept, we first obtained evidence that NACA influences neurophysiology in an amygdalar circuit. Then focusing on the amygdala, we were able to quantify a sex-specific persistent elevation in caspase activity in females after restraint stress. This simple in vivo caspase activity reporter will facilitate systems-level studies of apoptotic and nonapoptotic phenomena in behavioral and pathologic models.

Full Text

Duke Authors

Cited Authors

  • Nicholls, PJ; Pack, TF; Urs, NM; Kumar, S; Zhou, Y; Ichim, G; Ginzel, JD; Turu, G; Calabrese, E; Roberts, WL; Fan, P; Ostapchenko, VG; Guzman Lenis, MS; Beraldo, F; Hatina, J; Prado, VF; Prado, MAM; Spasojevic, I; Snyder, JC; Dzirasa, K; Johnson, GA; Caron, MG

Published Date

  • 2022

Published In

Volume / Issue

  • 9 / 5

PubMed ID

  • 36635920

Pubmed Central ID

  • PMC9536855

Electronic International Standard Serial Number (EISSN)

  • 2373-2822

Digital Object Identifier (DOI)

  • 10.1523/ENEURO.0147-21.2022

Language

  • eng

Conference Location

  • United States