南京神经内科与肿瘤药物开发国家重点实验室Chen Zhang，Xueyun Bi和温州医科大学Zi-Bing Jin共同合作，近期取得重要工作进展。他们研究发现，Timp1缺失能够诱导小鼠焦虑样行为。相关研究成果2023年12月19日在线发表于《神经科学通报》杂志上。

据介绍，海马体对学习和记忆至关重要，除此之外，它在调节情绪行为方面也发挥着重要作用，因为海马体的兴奋性和可塑性会影响焦虑和恐惧。脑突触可塑性可能受到基质金属蛋白酶组织抑制剂1（TIMP1）的调节，TIMP1是一种已知的细胞外基质蛋白抑制剂，海马中TIMP1的表达可由神经元兴奋和各种刺激诱导。然而，Timp1在恐惧学习、焦虑和海马突触功能中的参与仍有待确定。

研究人员对Timp1在体内功能的研究表明，Timp1敲除小鼠表现出焦虑样行为，但正常的恐惧学习。电生理学结果表明，Timp1敲除小鼠在腹侧CA1区表现出高活跃性，但在Schaffer侧支通路中基本的突触传递和可塑性是正常的。

总之，这一研究结果表明，体内Timp1的缺失会导致焦虑行为的发生，但Timp1对恐惧学习并不重要。

附：英文原文

Title: Timp1 Deletion Induces Anxiety-like Behavior in Mice

Author: Wang, Xiaotong, Zheng, Wei, Zhu, Ziyi, Xing, Biyu, Yan, Weijie, Zhu, Ke, Xiao, Lingli, Yang, Chaojuan, Wei, Mengping, Yang, Lei, Jin, Zi-Bing, Bi, Xueyun, Zhang, Chen

Issue&Volume: 2023-12-19

Abstract: The hippocampus is essential for learning and memory, but it also plays an important role in regulating emotional behavior, as hippocampal excitability and plasticity affect anxiety and fear. Brain synaptic plasticity may be regulated by tissue inhibitor of matrix metalloproteinase 1 (TIMP1), a known protein inhibitor of extracellular matrix (ECM), and the expression of TIMP1 in the hippocampus can be induced by neuronal excitation and various stimuli. However, the involvement of Timp1 in fear learning, anxiety, and hippocampal synaptic function remains to be established. Our study of Timp1 function in vivo revealed that Timp1 knockout mice exhibit anxiety-like behavior but normal fear learning. Electrophysiological results suggested that Timp1 knockout mice showed hyperactivity in the ventral CA1 region, but the basic synaptic transmission and plasticity were normal in the Schaffer collateral pathway. Taken together, our results suggest that deletion of Timp1 in vivo leads to the occurrence of anxiety behaviors, but that Timp1 is not crucial for fear learning.

DOI: 10.1007/s12264-023-01163-1

Source: https://link.springer.com/article/10.1007/s12264-023-01163-1