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Research Paper|Volume 15, Issue 24|pp 15324—15339

Parvalbumin interneurons dysfunction is potentially associated with FαMNs decrease and NRG1-ErbB4 signaling inhibition in spinal cord in amyotrophic lateral sclerosis

Qin Kang1,2, Shishi Jiang1, Jun Min3, Fan Hu2, Renshi Xu1,2
  • 1Department of Neurology, Medical College of Nanchang University, Nanchang 330006, Jiangxi, P.R. China
  • 2Department of Neurology, Jiangxi Provincial People’s Hospital, First Affiliated Hospital of Nanchang Medical College, Clinical College of Nanchang Medical College, Nanchang 330006, Jiangxi, P.R. China
  • 3Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, P.R. China
* Equal contribution and share first authorship
Received: May 11, 2023Accepted: November 6, 2023Published: December 28, 2023
https://doi.org/10.18632/aging.205351

Copyright: © 2023 Kang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Objective: To investigate the alteration of PV interneurons in ALS mainly focusing its dynamic changes and its relationship with motor neurons and ErbB4 signaling.

Methods: SOD1G93A mice were used as ALS model. ALS animals were divided into different groups according to birth age: symptomatic prophase (50~60 days), symptomatic phase (90~100 days), and symptomatic progression (130~140 days). Immunofluorescence was performed for measurement of PV-positive interneurons, MMP-9, ChAT, NeuN and ErbB4. RT-qPCR and western blot were used to determine the expression of PV and MMP-9.

Results: PV expression was remarkably higher in the anterior horn of gray matter compared with posterior horn and area in the middle of gray matter in control mice. In ALS mice, PV, MMP-9 and ErbB4 levels were gradually decreased along with onset. PV, MMP-9 and ErbB4 levels in ALS mice were significantly down-regulated than control mice after onset, indicating the alteration of PV interneurons, FαMNs and ErbB4. SαMNs levels only decreased remarkably at symptomatic progression in ALS mice compared with control mice, while γMNs levels showed no significant change during whole period in all mice. MMP-9 and ErbB4 were positively correlated with PV. NRG1 treatment significantly enhanced the expression of ErBb4, PV and MMP-9 in ALS mice.

Conclusion: PV interneurons decrease is along with FαMNs and ErbB4 decrease in ALS mice.