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Effects of the Notch Signaling Pathway on Secondary Brain Changes Caused by Spinal Cord Injury in Mice

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Abstract

Spinal cord injury (SCI) can cause secondary brain changes, leading to hypomyelination in the dorsolateral prefrontal cortex (dlPFC). Some studies have shown that notch signaling pathway activation can regulate oligodendrocyte maturation and myelination. The aim of this study was to investigate whether inhibition of the Notch signaling pathway can alleviate hypomyelination in the dlPFC caused by SCI. Moreover, we further investigated whether the changes in myelination in the dlPFC are associated with neuropathic pain following SCI. We established a mouse model of SCI and observed the changes in mechanical and thermal hyperalgesia. Western blotting and immunofluorescence were used to analyze the changes in myelination in the dlPFC. The results indicated the existence of a relationship between activation of the Notch signaling pathway and hypomyelination in the dlPFC and confirmed the existence of a relationship between hypomyelination in the dlPFC and decreases in mechanical and thermal hyperalgesia thresholds. In conclusion, these results suggested that the Notch signaling pathway is activated after SCI, leading to hypomyelination in the dlPFC, and that DAPT can inhibit the Notch signaling pathway and improve mechanical and thermal hyperalgesia thresholds. Our findings provide a new target for the treatment of neuropathic pain caused by SCI.

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Data Availability

Data and materials are available from the corresponding author on reasonable request.

Abbreviations

SCI:

Spinal cord injury

dlPFC:

Dorsolateral prefrontal cortex

CNS:

Central nervous system

NICD:

Notch intracellular domain

BMS:

Basso mouse scale

PWT:

Paw withdrawal threshold

PWL:

Paw withdrawal latency

BSA:

Bovine serum albumin

Olig2:

Oligodendrocyte transcription factor 2

MBP:

Myelin basic protein

PS1:

Presenilin1

Aβ:

β-Amyloid peptide protein

APP:

Amyloid precursor protein

CNPase:

2′,3′-Cyclic nucleotide phosphohydrolase

PLP:

Proteolipid protein

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Acknowledgements

We thank the Basic Medicine Center of the Jiujiang University, China, for the access to equipment. The English language was corrected and certified by aje.com.

Funding

This work was supported by the National Natural Science Foundation of China (NSFC; Grant No. 81860225).

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Authors and Affiliations

  1. Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, NO17 Yong Wai Zheng Street, Nanchang, 330006, Jiangxi, People’s Republic of China

    Chengcai Li, Wu Zhou, Zhiping Xie, Shenke Xie & Meihua Li

  2. School of Basic Medicine, Jiujiang University, Jiujiang, 332005, Jiangxi, People’s Republic of China

    Shaoxin Huang

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  1. Chengcai Li
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Correspondence to Meihua Li.

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Li, C., Huang, S., Zhou, W. et al. Effects of the Notch Signaling Pathway on Secondary Brain Changes Caused by Spinal Cord Injury in Mice. Neurochem Res 47, 1651–1663 (2022). https://doi.org/10.1007/s11064-022-03558-4

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  • DOI: https://doi.org/10.1007/s11064-022-03558-4

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