The role of PTEN in primary sensory neurons in processing itch and thermal information in mice

Ling Hu; Guan-Yu Jiang; Ying-Ping Wang; Zhi-Bin Hu; Bing-Yao Zhou; Lei Zhang; Ning-Ning Song; Ying Huang; Guo-Dong Chai; Jia-Yin Chen; Bing Lang; Lin Xu; Jun-Ling Liu; Yong Li; Qing-Xiu Wang; Yu-Qiang Ding

doi:10.1016/j.celrep.2022.110724

The role of PTEN in primary sensory neurons in processing itch and thermal information in mice

Cell Rep. 2022 Apr 19;39(3):110724. doi: 10.1016/j.celrep.2022.110724.

Authors

Ling Hu¹, Guan-Yu Jiang², Ying-Ping Wang³, Zhi-Bin Hu⁴, Bing-Yao Zhou⁴, Lei Zhang², Ning-Ning Song⁵, Ying Huang⁶, Guo-Dong Chai⁷, Jia-Yin Chen⁸, Bing Lang⁹, Lin Xu¹⁰, Jun-Ling Liu³, Yong Li³, Qing-Xiu Wang¹¹, Yu-Qiang Ding¹²

Affiliations

¹ Department of Laboratory Animal Science, Fudan University, Shanghai 200032, China; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China; Key Laboratory of Arrhythmias, Ministry of Education, East Hospital, and Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai 200092, China.
² Key Laboratory of Arrhythmias, Ministry of Education, East Hospital, and Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai 200092, China.
³ Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Institute of Medical Sciences, Shanghai JiaoTong University School of Medicine, Shanghai 200025, China.
⁴ State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China.
⁵ Department of Laboratory Animal Science, Fudan University, Shanghai 200032, China; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China.
⁶ Department of Laboratory Animal Science, Fudan University, Shanghai 200032, China.
⁷ Department of Anesthesiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
⁸ Department of Laboratory Animal Science, Fudan University, Shanghai 200032, China; Key Laboratory of Arrhythmias, Ministry of Education, East Hospital, and Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai 200092, China.
⁹ Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
¹⁰ Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
¹¹ Department of Anesthesiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. Electronic address: qxw1123@126.com.
¹² Department of Laboratory Animal Science, Fudan University, Shanghai 200032, China; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China; Key Laboratory of Arrhythmias, Ministry of Education, East Hospital, and Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai 200092, China. Electronic address: dingyuqiang@vip.163.com.

PMID: 35443189
DOI: 10.1016/j.celrep.2022.110724

Abstract

PTEN is known as a tumor suppressor and plays essential roles in brain development. Here, we report that PTEN in primary sensory neurons is involved in processing itch and thermal information in adult mice. Deletion of PTEN in the dorsal root ganglia (DRG) is achieved in adult Drg11-Cre^ER: PTEN^flox/flox (PTEN CKO) mice with oral administration of tamoxifen, and CKO mice develop pathological itch and elevated itch responses on exposure to various pruritogens. PTEN deletion leads to ectopic expression of TRPV1 and MrgprA3 in IB4⁺ non-peptidergic DRG neurons, and the TRPV1 is responsive to capsaicin. Importantly, the elevated itch responses are no longer present in Drg11-Cre^ER: PTEN^flox/flox: TRPV1^flox/flox (PTEN: TRPV1 dCKO) mice. In addition, thermal stimulation is enhanced in PTEN CKO mice but blunted in dCKO mice. PTEN-involved regulation of itch-related gene expression in DRG neurons provides insights for understanding molecular mechanism of itch and thermal sensation at the spinal level.

Keywords: CP: Neuroscience; PTEN; TRPV1; adult gene deletion; itch; primary sensory neurons.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Capsaicin / pharmacology
Ganglia, Spinal / metabolism
Mice
Mice, Inbred C57BL
Pruritus* / pathology
Sensory Receptor Cells / metabolism
TRPV Cation Channels* / genetics
TRPV Cation Channels* / metabolism

Substances

TRPV Cation Channels
Capsaicin