Xu‑An Wang1  · Qing‑Ya Wu2  · Xiao‑Yu Shi3  · Xiao‑Peng Wang1  · Yan‑Yan Gao1  · Wei‑Wei Zhang1  · Yi‑Sheng Lu4  · Dan Liu5  · Ling‑Qiang Zhu6  · Hua Zheng2

1 Department of Anesthesiology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan 030032, China 

2 Department of Anesthesiology, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, and Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China 

3 Department of Conservative Dentistry and Endodontics, Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Shanxi Medical University School and Hospital of Stomatology, Taiyuan 030001, China 

4 Department of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China 

5 Department of Medical Genetics, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China 

6 Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

Abstract

Perioperative neurocognitive disorders (PND) encompass a spectrum of cognitive impairments that emerge during the perioperative period. The pathogenesis of PND is multifactorial, involving complex interactions between neuroinflammation, impairment of synaptic plasticity, dysregulation of brain-derived neurotrophic factor (BDNF) signaling, oxidative stress, and mitochondrial dysfunction. RNA splicing is increasingly recognized as a critical player in nervous system function and dysfunction. In this review, we explore the role of RNA splicing in modulating the major pathogenic mechanisms of PND. We highlight how aberrant splicing events promote neuroinflammation by altering the expression of pro-inflammatory genes, disrupt synaptic plasticity by modifying the profiles of synaptic proteins and neurotransmitter receptors, and impair the expression and function of BDNF. Additionally, RNA splicing abnormalities exacerbate oxidative stress and mitochondrial dysfunction, further amplifying neuronal damage. By elucidating the intricate interactions between RNA splicing and these core pathological processes, this review reveals the close association between RNA splicing dysregulation and the molecular underpinnings of PND, and highlights its potential regulatory role in PND pathogenesis.

Keywords

Perioperative neurocognitive disorders; RNA splicing; Neuroinflammation; Synaptic plasticity; BDNF; Oxidative stress; Mitochondrial dysfunction

[SpringerLink]