1. Measuring Nonapoptotic Caspase Activity with a Transgenic Reporter in Mice.
- Author
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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, and Caron MG
- Subjects
- Male, Female, Mice, Animals, Mice, Transgenic, Neuronal Plasticity, Caspase 9, Apoptosis physiology, Brain
- Abstract
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., (Copyright © 2022 Nicholls et al.)
- Published
- 2022
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