Journal
ENEURO
Volume 9, Issue 5, Pages -Publisher
SOC NEUROSCIENCE
DOI: 10.1523/ENEURO.0147-21.2022
Keywords
caspases; in vivo reporter; nonapoptotic; mapping; amygdala; stress; sex differences
Categories
Funding
- National Institutes of Health [1R21NS081513, 8P41EB015897, 2R01MH079201, 5R37MH073853]
- Canadian Institutes of Health Research Grants [MOP 93651, 12600, 89919]
- Pall Family Foundation
- National Institute of Mental Health's Psychoactive Drug Screening Program [HHSN-271-2013-00017-C.]
- Lennon Family Foundation
Ask authors/readers for more resources
In this study, a transgenic mouse was generated as a tool to map and quantify nonapoptotic caspase activity. It was found that nonapoptotic caspase activity influences neurophysiology and exhibits persistent elevation in response to restraint stress.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available