Multiple brain regions are involved in reaction to acute restraint stress in CYLD-knockout mice

Abstract

The lysine 63 deubiquitinase cylindromatosis (CYLD) is expressed at high levels in the brain and is considered to be involved in anxious and depressive behavior, cognitive inflexibility, and autism disorders. Previous research was limited in some brain regions, including the hippocampus, striatum, and amygdala. To better understand whether CYLD plays a role in adaptation to stress and which brain regions are involved, we analyzed the behavior of CYLD-knockout mice in the elevated plus maze (EPM) and light-dark box test (LDT) after acute restraint stress (ARS) and mapped their c-Fos immunoreactivity in brain sections. Here we report that CYLD deficiency leads to an unexpected reaction to ARS in mice, and is accompanied by significant neuronal activation of brain regions including the medial prefrontal cortex (mPFC), dorsal striatum (DS), nucleus accumbens (NAc), and basal lateral amygdala (BLA), but not ventral hippocampus (vHPC). Our findings show that CYLD participates in ARS-induced anxious behavior and that this involves multiple brain regions.

Keywords:

• Stress
• CYLD
• anxiety
• c-Fos

Author contributions

Yuan-Yuan HAN designed and performed immunostaining and behavioral experiments. Jian-Wen ZHOU and Zhi-Wei GUO conducted elevated-plus maze test. Zhuo-Qing WU and Zai-yong Zhang conducted c-Fos photographing and calculation. Yuan-Yuan HAN analyzed the data and wrote the paper. De-Xiang provided with suggestions on manuscript. Cheng LONG supervised the study, designed experiments and critical revision of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by grants from China Postdoctoral Science Foundation (2021M700933), the National Natural Science Foundation of China (31871170, 31970915, 32170950), and the Natural Science Foundation of the Guangdong Province (2021A1515010804).

Notes on contributors

Yuan-Yuan Han

Yuan-Yuan Han Ph.D graduated from South China Normal University, majoring in Neurobiology. She is currently doing postdoctoral research in Guangzhou Panyu District Hospital, who focuses on the immune and neural mechanisms of mental illness.

Jian-Wen Zhou

Jian-Wen Zhou is studying for a master’s degree at South China Normal University, who focus the regulation of striatum CYLD in anxiety.

Zhi-Wei Guo

Zhi-Wei Guo is a bachelor in South China Normal University, who studies anxiety and depression in mouse model of breast cancer.

Zhuo-Qing Wu

Zhuo-Qing Wu is studying for a master’s degree at South China Normal University, who mainly studies biology teaching.

Zai-Yong Zhang

Zai-Yong Zhang, Ph.D is the deputy chief physician of Guangzhou Panyu District Hospital, and he studies on coronary heart disease intervention and comprehensive management of heart patients.

De-xiang Liu

De-Xiang Liu is the chief physician of Guangzhou Panyu District Hospital, who specializes in magnetic resonance techniques and diagnostics.

Cheng Long

Cheng Long, Ph.D is a professor at South China Normal University, who focuses on neurodegenerative diseases and neural signal transduction. He presided over the National Natural Science Foundation of China, Guangdong Provincial Natural Science Foundation, Guangdong Provincial Department of Education Intelligence Introduction Special Project and Guangdong Provincial Department of Education Graduate Demonstration Course and other projects. He has published more than 80 research papers in domestic and foreign academic journals.