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Timp1 Deletion Induces Anxiety-like Behavior in Mice

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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.

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Acknowledgements

This work was supported by grants from the Key-Area Research and Development Program of Guangdong Province (2019B030335001); the National Natural Science Foundation of China (81925011, 92149304, and 32200636); the R&D Program of Beijing Municipal Education Commission (KM202310025028) and the High-Level Teachers project (CIT&TCD20190334); and the Youth Beijing Scholars Program (015).

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  1. Xiaotong Wang, Wei Zheng, Ziyi Zhu, Biyu Xing, and Weijie Yan contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Neurology and Oncology Drug Development, Nanjing, 210000, China

    Xiaotong Wang, Wei Zheng, Ziyi Zhu, Ke Zhu, Mengping Wei, Lei Yang, Xueyun Bi & Chen Zhang

  2. School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, 325035, China

    Biyu Xing, Lingli Xiao & Zi-Bing Jin

  3. School of Basic Medical Sciences, Beijing Key Laboratory of Neural Regeneration and Repair, Advanced Innovation Center for Human Brain Protection, Beijing Laboratory of Oral Health, Capital Medical University, Beijing, 100069, China

    Xiaotong Wang, Wei Zheng, Ziyi Zhu, Weijie Yan, Ke Zhu, Mengping Wei, Lei Yang, Xueyun Bi & Chen Zhang

  4. Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, 100005, China

    Zi-Bing Jin

  5. Chinese Institute for Brain Research, Beijing, 102206, China

    Chen Zhang

  6. Key Laboratory for Biomechanics and Mechanobiology of the Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Engineering Medicine, Beihang University, Beijing, 100191, China

    Chaojuan Yang

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  1. Xiaotong Wang
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Wang, X., Zheng, W., Zhu, Z. et al. Timp1 Deletion Induces Anxiety-like Behavior in Mice. Neurosci. Bull. (2023). https://doi.org/10.1007/s12264-023-01163-1

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