郑州大学许继田研究组取得一项新突破。他们提出了通过降低CPEB3泛素化下调海马CA1中的Neuralized1介导神经性疼痛的突触可塑性损伤和认知缺陷。2025年11月18日出版的《神经科学通报》发表了这项成果。

在本研究中，课题组研究人员发现雄性大鼠引起的神经性疼痛发生腰脊神经结扎（SNL）后会出现学习记忆缺陷和海马LTP损伤。SNL后海马CA1中Neurl1的表达降低。这种减少与泛素化CPEB3水平的降低和GluA1和GluA2的产生减少是平行的。在CA1中过度表达Neurl1可以挽救认知缺陷和LTP损伤，并逆转SNL后泛素化CPEB3水平的降低和GluA1和GluA2产生的减少。双侧海马CA1中Neurl1或CPEB3的特异性下调导致大鼠认知缺陷和突触可塑性损伤。SNL前Neurl1过表达治疗所恢复的认知功能和突触可塑性被CA1中CPEB3的下调所抵消。综上所述，上述结果表明，通过降低CPEB3泛素化而下调Neurl1，进而抑制GluA1和GluA2的产生，介导海马CA1突触可塑性损伤，导致神经性疼痛认知缺陷的发生。

研究人员表示，神经性疼痛常与认知缺陷合并症。神经化1 （Neuralized1）介导的海马CPEB3泛素化对学习和记忆至关重要。然而，Neurl1在神经性疼痛认知障碍中的作用仍不清楚。

附：英文原文

Title: Downregulation of Neuralized1 in the Hippocampal CA1 Through Reducing CPEB3 Ubiquitination Mediates Synaptic Plasticity Impairment and Cognitive Deficits in Neuropathic Pain

Author: Gao, Yan, Qiao, Yiming, Wang, Xueli, Zhu, Manyi, Yu, Lili, Yuan, Haozhuang, Li, Liren, Hu, Nengwei, Xu, Ji-Tian

Issue&Volume: 2025-11-18

Abstract: Neuropathic pain is frequently comorbidity with cognitive deficits. Neuralized1 (Neurl1)-mediated ubiquitination of CPEB3 in the hippocampus is critical in learning and memory. However, the role of Neurl1 in the cognitive impairment in neuropathic pain remains elusive. Herein, we found that lumbar 5 spinal nerve ligation (SNL) in male rat-induced neuropathic pain was followed by learning and memory deficits and LTP impairment in the hippocampus. The Neurl1 expression in the hippocampal CA1 was decreased after SNL. And this decrease paralleled the reduction of ubiquitinated-CPEB3 level and reduced production of GluA1 and GluA2. Overexpression of Neurl1 in the CA1 rescued cognitive deficits and LTP impairment, and reversed the reduction of ubiquitinated-CPEB3 level and the decrease of GluA1 and GluA2 production following SNL. Specific knockdown of Neurl1 or CPEB3 in bilateral hippocampal CA1 in nave rats resulted in cognitive deficits and impairment of synaptic plasticity. The rescued cognitive function and synaptic plasticity by the treatment of overexpression of Neurl1 before SNL were counteracted by the knockdown of CPEB3 in the CA1. Collectively, the above results suggest that the downregulation of Neurl1 through reducing CPEB3 ubiquitination and, in turn, repressing GluA1 and GluA2 production and mediating synaptic plasticity impairment in hippocampal CA1 leads to the genesis of cognitive deficits in neuropathic pain.

DOI: 10.1007/s12264-025-01536-8

Source: https://link.springer.com/article/10.1007/s12264-025-01536-8