Journal Article

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

Song, Jin-Xiu, Qi, Su-Hua, Li, Li-Li, Liang, Zhi-Yan, Wullaert, Andy, Zhu, Hai-Xue, Chen, Jie, Wang, Wan, Hu, Zhao-Li, Li, Yu-Jie, Huang, Lin-Yan, Liu, Yi-Ning, Demon, Dieter

2025

Overview

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.

• Publisher: Springer US,Springer Nature B.V
• Subject: Animals / Behavior, Animal / Biomedical and Life Sciences / Biomedicine / Brain-derived neurotrophic factor / Brain-Derived Neurotrophic Factor - metabolism / c-Fos protein / Caspase 12 - deficiency / Caspase 12 - metabolism / Caspase-12 / Cell Biology / Cell death / Cerebellum / Cerebellum - metabolism / Cerebellum - pathology / Hyperactivity / Kinases / Male / Mental Disorders - enzymology / Mental Disorders - prevention & control / Mice / Mice, Inbred C57BL / Motor Activity / Neurobiology / Neurology / Neurons / Neurosciences / Protein-tyrosine kinase receptors / Purkinje cells / Purkinje Cells - enzymology / Purkinje Cells - metabolism / Purkinje Cells - pathology / Signal Transduction