Caspase-12 is Expressed in Purkinje Neurons and Prevents Psychiatric-Like Behavior in Mice.

Autor: Huang LY; School of Medical Technology, Xuzhou Key Laboratory of Laboratory Diagnostics, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, People's Republic of China.; VIB Center for Inflammation Research, Zwijnaarde, Belgium.; Department of Internal Medicine and Paediatrics, Ghent University, Ghent, Belgium., Liu YN; School of Medical Technology, Xuzhou Key Laboratory of Laboratory Diagnostics, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, People's Republic of China., Chen J; School of Medical Technology, Xuzhou Key Laboratory of Laboratory Diagnostics, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, People's Republic of China.; Department of Laboratory Medicine, The Affiliated Hospital of Xuzhou Medical University, Huaihai West Road 99, Xuzhou, 221002, China., Zhu HX; Department of Ophthalmology, The Affiliated Huai'an Hospital of Xuzhou Medical University, No.62 Huaihai South Road, Huai'an, 223001, Jiangsu, People's Republic of China., Li LL; School of Medical Technology, Xuzhou Key Laboratory of Laboratory Diagnostics, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, People's Republic of China., Liang ZY; School of Medical Technology, Xuzhou Key Laboratory of Laboratory Diagnostics, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, People's Republic of China., Song JX; Department of Pharmacology, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, People's Republic of China., Li YJ; Department of Clinical Laboratory, Kunshan First People's Hospital, Kunshan, Jiangsu, 215300, People's Republic of China., Hu ZL; Research Center for Biochemistry and Molecular Biology and Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical University, Xuzhou, People's Republic of China., Demon D; VIB Center for Inflammation Research, Zwijnaarde, Belgium.; Department of Internal Medicine and Paediatrics, Ghent University, Ghent, Belgium., Wullaert A; VIB Center for Inflammation Research, Zwijnaarde, Belgium.; Department of Internal Medicine and Paediatrics, Ghent University, Ghent, Belgium.; Cell Death Signaling Lab, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium., Wang W; School of Medical Technology, Xuzhou Key Laboratory of Laboratory Diagnostics, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, People's Republic of China., Qi SH; School of Medical Technology, Xuzhou Key Laboratory of Laboratory Diagnostics, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, People's Republic of China. suhuaqi@xzhmu.edu.cn.
Jazyk: angličtina
Zdroj: Molecular neurobiology [Mol Neurobiol] 2024 Jul 18. Date of Electronic Publication: 2024 Jul 18.
DOI: 10.1007/s12035-024-04356-5
Abstrakt: Caspase-12 is a caspase family member for which functions in regulating cell death and inflammation have previously been suggested. In this study, we used caspase-12 lacZ reporter mice to elucidate the expression pattern of caspase-12 in order to obtain an idea about its possible in vivo function. Strikingly, these reporter mice showed that caspase-12 is expressed explicitly in Purkinje neurons of the cerebellum. As this observation suggested a function for caspase-12 in Purkinje neurons, we analyzed the brain and behavior of caspase-12 deficient mice in detail. Extensive histological analyses showed that caspase-12 was not crucial for establishing cerebellum structure or for maintaining Purkinje cell numbers. We then performed behavioral tests to investigate whether caspase-12 deficiency affects memory, motor, and psychiatric functions in mice. Interestingly, while the absence of caspase-12 did not affect memory and motor function, caspase-12 deficient mice showed depression and hyperactivity tendencies, together resembling manic behavior. Next, suggesting a possible molecular mechanistic explanation, we showed that caspase-12 deficient cerebella harbored diminished signaling through the brain-derived neurotrophic factor/tyrosine kinase receptor B/cyclic-AMP response binding protein axis, as well as strongly enhanced expression of the neuronal activity marker c-Fos. Thus, our study establishes caspase-12 expression in mouse Purkinje neurons and opens novel avenues of research to investigate the role of caspase-12 in regulating psychiatric behavior.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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