Measuring Nonapoptotic Caspase Activity with a Transgenic Reporter in Mice.

Autor:	Nicholls PJ; Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710 peter.nicholls@duke.edu., Pack TF; Department of Cell Biology, Duke University Medical Center, Durham, NC 27710.; Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710., Urs NM; Department of Cell Biology, Duke University Medical Center, Durham, NC 27710., Kumar S; Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710., Zhou Y; Department of Cell Biology, Duke University Medical Center, Durham, NC 27710., Ichim G; Center for Research on Cancer in Lyon, University of Lyon, Lyon 69008, France., Ginzel JD; Department of Cell Biology, Duke University Medical Center, Durham, NC 27710., Turu G; Department of Cell Biology, Duke University Medical Center, Durham, NC 27710., Calabrese E; Department of Biomedical Engineering, Duke University Medical Center, Durham, NC 27710.; Center for In Vivo Microscopy, Department of Radiology, Duke University Medical Center, Durham, NC 27710., Roberts WL; Department of Cell Biology, Duke University Medical Center, Durham, NC 27710., Fan P; Department of Medicine, Duke University Medical Center, Durham, NC 27710., Ostapchenko VG; Robarts Research Institute, University of Western Ontario, London, Ontario N6A 3K7, Canada., Guzman Lenis MS; Robarts Research Institute, University of Western Ontario, London, Ontario N6A 3K7, Canada.; Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario N6A 3K7, Canada., Beraldo F; Robarts Research Institute, University of Western Ontario, London, Ontario N6A 3K7, Canada.; Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario N6A 3K7, Canada., Hatina J; Institute of Biology, Charles University, Plzen CZ-32300, Czech Republic., Prado VF; Robarts Research Institute, University of Western Ontario, London, Ontario N6A 3K7, Canada.; Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario N6A 3K7, Canada.; Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario N6A 3K7, Canada., Prado MAM; Robarts Research Institute, University of Western Ontario, London, Ontario N6A 3K7, Canada.; Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario N6A 3K7, Canada.; Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario N6A 3K7, Canada., Spasojevic I; Department of Medicine, Duke University Medical Center, Durham, NC 27710., Snyder JC; Department of Cell Biology, Duke University Medical Center, Durham, NC 27710.; Department of Surgery, Duke University Medical Center, Durham, NC 27710., Dzirasa K; Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710.; Department of Biomedical Engineering, Duke University Medical Center, Durham, NC 27710.; Department of Neurobiology, Duke University Medical Center, Durham, NC 27710., Johnson GA; Department of Biomedical Engineering, Duke University Medical Center, Durham, NC 27710.; Center for In Vivo Microscopy, Department of Radiology, Duke University Medical Center, Durham, NC 27710.; Department of Physics, Duke University, Durham, NC 27710., Caron MG; Department of Cell Biology, Duke University Medical Center, Durham, NC 27710.; Department of Medicine, Duke University Medical Center, Durham, NC 27710.; Department of Neurobiology, Duke University Medical Center, Durham, NC 27710.
Jazyk:	angličtina
Zdroj:	ENeuro [eNeuro] 2022 Oct 04; Vol. 9 (5). Date of Electronic Publication: 2022 Oct 04 (Print Publication: 2022).
DOI:	10.1523/ENEURO.0147-21.2022
Abstrakt:	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.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu