Reversing anxiety by targeting a stress- responsive signaling pathway

• 成果类型: Article
• 署名作者: Pandey, Saurabh; Han, Wenyan; Li, Jun; Shepard, Ryan; Wu, Kunwei; Castellano, David; Tian, Qingjun; Dong, Lijin; Li, Yan; Lu, Wei
• 署名单位: National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS); National Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI); National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14165
• DOI: 10.1073/pnas.2400078121
• 发表日期: 2024-07-30
• 关键词: neuroligin 2; griscelli-syndrome; DEPRESSION; calmodulin; deficits

摘要

Current treatments of anxiety and depressive disorders are plagued by considerable side effects and limited efficacies, underscoring the need for additional molecular targets that can be leveraged to improve medications. Here, we have identified a molecular cascade triggered by chronic stress that exacerbates anxiety- and depressive- like behaviors. Specifically, chronic stress enhances Src kinase activity and tyrosine phosphorylation of resulting in decreased inhibitory transmission and heightened anxiety- like behaviors. and effectively reverses heightened anxiety- like behaviors in chronically stressed mice, a process requiring the MyoVa-NL2 interaction. These data demonstrate the reversibility of anxiety- and depressive- like phenotypes at both molecular and behavioral levels and uncover a therapeutic target for anxiety and depressive disorders.