2. Academic Validation
  3. Excessive calpain impairs offspring cognition via BDNF/TrkB dysregulation after maternal non-obstetric surgery during pregnancy

Excessive calpain impairs offspring cognition via BDNF/TrkB dysregulation after maternal non-obstetric surgery during pregnancy

  • Neuropharmacology. 2025 Dec 15:281:110701. doi: 10.1016/j.neuropharm.2025.110701.
Nannan Zhang 1,  Mengdie Wang 2,  Jia Qin 2,  Wei Zeng 2,  Jiafeng Fu 3,  Yanfei Lu 3,  Hongfa Wang 3,  Qiang Ma 2,  Foquan Luo 4
Affiliations

Affiliations

  • 1 Gannan Medical University, Ganzhou, Jiangxi, 341000, China; Center for Rehabilitation Medicine, Department of Anesthesiology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, China; Research Institute of Anesthesiology and Perioperative Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, 310053, China.
  • 2 Center for Rehabilitation Medicine, Department of Anesthesiology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, China.
  • 3 Center for Rehabilitation Medicine, Department of Anesthesiology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, China; Research Institute of Anesthesiology and Perioperative Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, 310053, China.
  • 4 Center for Rehabilitation Medicine, Department of Anesthesiology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, China; Research Institute of Anesthesiology and Perioperative Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, 310053, China. Electronic address: lfqxmc@ncu.edu.cn.
PMID: 41043554 DOI: 10.1016/j.neuropharm.2025.110701
Abstract

Maternal non-obstetric surgery during pregnancy has been linked to adverse neurodevelopmental outcomes in offspring, but the underlying mechanisms remain poorly understood. This study investigated how excessive calpain activity disrupts hippocampal development and impairs cognition by suppressing the BDNF/TrkB signaling pathway in a Sprague-Dawley pregnant rat model. We revealed that maternal surgery impaired spatial learning and contextual fear memory in offspring, whereas propofol alone had no such effect. These deficits were accompanied by reduced hippocampal dendritic spine density, decreased NeuN expression, and downregulation of PSD95, BDNF, TrkB, and phosphorylated TrkB proteins. Notably, calpain activity was significantly increased following surgery. Postnatal administration of calpain inhibitor MDL 28170 or TrkB Agonist 7,8-DHF partially restored protein expression levels, alleviated dendritic and neuronal structure, and improved cognitive performance. These findings indicate that excessive calpain activation impairs offspring cognition by disrupting BDNF/TrkB-mediated synaptic plasticity and neuronal integrity. Pharmacological inhibition of calpain or activation of TrkB may serve as potential therapeutic strategies to mitigate neurodevelopmental damage caused by maternal surgery during pregnancy.

Keywords

Calpain; Cognitive impairment; Propofol; Third trimester; TrkB.

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