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Dysfunction of NRG1/ErbB4 Signaling in the Hippocampus Might Mediate Long-term Memory Decline After Systemic Inflammation

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Abstract

Accumulating evidence has suggested that a great proportion of sepsis survivors suffer from long-term cognitive impairments after hospital discharge, leading to decreased life quality and substantial caregiving burdens for family members. However, the underlying mechanism remains unclear. In the present study, we established a mouse model of systemic inflammation by repeated lipopolysaccharide (LPS) injections. A combination of behavioral tests, biochemical, and in vivo electrophysiology techniques were conducted to test whether abnormal NRG1/ErbB4 signaling, parvalbumin (PV) interneurons, and hippocampal neural oscillations were involved in memory decline after repeated LPS injections. Here, we showed that LPS induced long-term memory decline, which was accompanied by dysfunction of NRG1/ErbB4 signaling and PV interneurons, and decreased theta and gamma oscillations. Notably, NRG1 treatment reversed LPS-induced decreases in p-ErbB4 and PV expressions, abnormalities in theta and gamma oscillations, and long-term memory decline. Together, our study demonstrated that dysfunction of NRG1/ErbB4 signaling in the hippocampus might mediate long-term memory decline in a mouse model of systemic inflammation induced by repeated LPS injections. Thus, targeting NRG1/ErbB4 signaling in the hippocampus may be promising for the prevention and treatment of this long-term memory decline.

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Data Availability Statement

The data of this study are available from the corresponding author upon reasonable request.

Code Availability

Not applicable.

Abbreviations

LPS:

Lipopolysaccharide

NRG1:

Neuregulin-1

ICV:

Intracerebroventricular

PV:

Parvalbumin

ErbB4:

Tyrosine kinase receptor epidermal growth factor receptor 4

GABA:

Gamma aminobutyric acid

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Acknowledgements

The authors would like to thank the MARC of Nanjing University.

Funding

This work was supported by the grants from the National Natural Science Foundation of China (Nos., 81971020, 81971892, 82172131).

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Authors and Affiliations

  1. Department of Anesthesiology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China

    Yu-zhu Gao, Xin-miao Wu & Mu-huo Ji

  2. Department of Anesthesiology, Jinling Hospital, Nanjing University, Nanjing, China

    Zhi-qiang Zhou

  3. Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

    Pan-miao Liu & Jian-jun Yang

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  1. Yu-zhu Gao
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  2. Xin-miao Wu
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Contributions

YZG and XMW contributed to performing the experiment and writing the manuscript. ZQZ and PML established the animal model and analyzed the data. JJY and MHJ contributed to the design of experiment.

Corresponding authors

Correspondence to Jian-jun Yang or Mu-huo Ji.

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All the animal experiments were approved by the Ethics Committee of Nanjing Medical University, and all procedures were performed in accordance with the approved guidelines.

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Gao, Yz., Wu, Xm., Zhou, Zq. et al. Dysfunction of NRG1/ErbB4 Signaling in the Hippocampus Might Mediate Long-term Memory Decline After Systemic Inflammation. Mol Neurobiol 60, 3210–3226 (2023). https://doi.org/10.1007/s12035-023-03278-y

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