2. Academic Validation
  3. Protective role of TRPV2 in synaptic plasticity through the ERK1/2-CREB-BDNF pathway in chronic unpredictable mild stress rats

Protective role of TRPV2 in synaptic plasticity through the ERK1/2-CREB-BDNF pathway in chronic unpredictable mild stress rats

  • Biochem Biophys Res Commun. 2024 May 15:721:150128. doi: 10.1016/j.bbrc.2024.150128.
Yitong Zhou 1,  Ting Cong 2,  Jun Chen 3,  Zhenchen Chu 4,  Ye Sun 1,  Danmei Zhao 1,  Xue Chen 1,  Liya Li 1,  Yingxin Liu 5,  Jiani Cheng 1,  Qiwei Li 1,  Shengming Yin 6,  Zhaoyang Xiao 7
Affiliations

Affiliations

  • 1 Department of Anesthesiology, The Second Affliated Hospital of Dalian Medical University, 467 Zhongshan Road, Shahekou District, Dalian, 116027, Liaoning, China.
  • 2 Department of Anesthesiology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, China.
  • 3 Laboratory Animal Center of Dalian Medical University, Dalian, 116044, Liaoning, China.
  • 4 Department of Orthopedics, Qingdao Municipal Hospital, Qingdao, 266011, Shandong, China.
  • 5 Department of Physiology, Basic Medicine College of Dalian Medical University, No. 9, West Section, Lvshun South Road, Lvshunkou District, Dalian, 116044, Liaoning, China.
  • 6 Department of Physiology, Basic Medicine College of Dalian Medical University, No. 9, West Section, Lvshun South Road, Lvshunkou District, Dalian, 116044, Liaoning, China. Electronic address: dlshengming@163.com.
  • 7 Department of Anesthesiology, The Second Affliated Hospital of Dalian Medical University, 467 Zhongshan Road, Shahekou District, Dalian, 116027, Liaoning, China. Electronic address: xiaozhaoy2012@163.com.
PMID: 38776831 DOI: 10.1016/j.bbrc.2024.150128
Abstract

Purpose: Chronic stress is a significant risk factor for mood disorders such as depression, where synaptic plasticity plays a central role in pathogenesis. Transient Receptor Potential Vanilloid Type-2 (TRPV2) Ion Channels are implicated in hypothalamic-pituitary-adrenal axis disorders. Previous proteomic analysis indicated a reduction in TRPV2 levels in the chronic unpredictable mild stress (CUMS) rat model, yet its role in synaptic plasticity during depression remains to be elucidated. This study aims to investigate TRPV2's role in depression and its underlying mechanisms.

Methods: In vivo and in vitro experiments were conducted using the TRPV2-specific agonist probenecid and ERK1/2 inhibitors SCH772984. In vivo, rats underwent six weeks of CUMS before probenecid administration. Depressive-like behaviors were assessed through behavioral tests. ELISA kits measured 5-HT, DA, NE levels in rat hippocampal tissues. Hippocampal morphology was examined via Nissl staining. In vitro, rat hippocampal neuron cell lines were treated with ERK1/2 inhibitors SCH772984 and probenecid. Western blot, immunofluorescence, immunohistochemical staining, and RT-qPCR assessed TRPV2 expression, neurogenesis-related proteins, synaptic markers, and ERK1/2-CREB-BDNF signaling proteins.

Results: Decreased hippocampal TRPV2 levels were observed in CUMS rats. Probenecid treatment mitigated depressive-like behavior and enhanced hippocampal 5-HT, NE, and DA levels in CUMS rats. TRPV2 activation countered CUMS-induced synaptic plasticity inhibition. Probenecid activated the ERK1/2-CREB-BDNF pathway, suggesting TRPV2's involvement in this pathway via ERK1/2.

Conclusion: These findings indicate that TRPV2 activation offers protective effects against depressive-like behaviors and enhances hippocampal synaptic plasticity in CUMS rats via the ERK1/2-CREB-BDNF pathway. TRPV2 emerges as a potential therapeutic target for depression.

Keywords

CUMS; Depression; ERK1/2-CREB-BDNF signaling pathway; Synaptic plasticity; TRPV2.

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