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Perineuronal Nets Alterations Contribute to Stress-Induced Anxiety-Like Behavior

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Abstract

Anxiety disorder is one of the most common mental disorders worldwide, affecting nearly 30% of adults. However, its underlying molecular mechanisms are still unclear. Here we subjected mice to chronic restraint stress (CRS), a paradigm known to induce anxiety-like behavior in mice. CRS mice exhibited anxiety-like behavior and reduced synaptic transmission in the medial prefrontal cortex (mPFC). Notably, Wisteria Floribunda agglutinin (WFA) staining showed a reduction of perineuronal nets (PNNs) expression in the mPFC of CRS mice. And the mRNA and protein levels of aggrecan (ACAN), a core component of PNNs, were also reduced. Parallelly, enzymatic digestion of PNNs in the mPFC by injecting Chondroitinase ABC (chABC) resulted in anxiety-like behavior in mice. Fluoxetine (FXT) is a clinically prescribed antidepressant/anxiolytic drug. FXT treatment in CRS mice not only ameliorated their deficits in behavior and synaptic transmissions, but also prevented CRS-induced reduction of PNNs and ACAN expressions. This study demonstrates that proper PNNs level is critical to brain functions, and their decline may serve as a pathological mechanism of anxiety disorders.

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Data Availability

All data generated and analyzed in this study are available from the corresponding author on reasonable request.

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Acknowledgements

We would like to thank all the members in the lab for the constructive discussion.

Funding

This research was supported by grant from the National Natural Science Foundation of China (82271558).

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Author notes

  1. Xianghe Li and Dongyan Ren contributed equally to this work.

Authors and Affiliations

  1. Queen Mary School of Nanchang University, Nanchang, 330031, China

    Xianghe Li & Nuojing Li

  2. Institute of Life Science, Nanchang University, Nanchang, 330031, China

    Dongyan Ren, Bin Luo, Ziyang Liu & Erkang Fei

  3. School of Life Sciences, Nanchang University, Nanchang, 330031, China

    Dongyan Ren & Ziyang Liu

  4. School of Basic Medical Sciences, Nanchang University, Nanchang, 330031, China

    Tian Zhou

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  1. Xianghe Li
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Contributions

XL, DR and BL conceived and designed the research project. XL, DR, ZL, NL and BL performed experiments and collected the data. XL and DR analyzed the data. DR and XL prepared the figures. EF and DR wrote the manuscript. TZ provided technical and intellectual support. All authors provided critical reviews of the results and approved the manuscript.

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Correspondence to Erkang Fei.

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All animal protocols used in this study were approved by the Experimental Animal Welfare Ethics Committee of Nanchang University, in accordance with EN Directive 2010/63/EU on the protection of animals used for scientific purposes.

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Li, X., Ren, D., Luo, B. et al. Perineuronal Nets Alterations Contribute to Stress-Induced Anxiety-Like Behavior. Mol Neurobiol 61, 411–422 (2024). https://doi.org/10.1007/s12035-023-03596-1

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