Targeting of MALT1 May Improve Functional Recovery and Attenuate Microglia M1 Polarization-Mediated Neuroinflammation During Spinal Cord Injury.

Abstract

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is involved in neural injury, neuroinflammation, microglia activation, and polarization, while its function in spinal cord injury (SCI) remains unclear. Thus, this study aimed to evaluate the role of MALT1 modification on SCI recovery and its underlying mechanism. SCI surgery or sham surgery was performed in Sprague-Dawley rats. Then, MALT1 knockdown or negative control lentivirus was injected into SCI rats. Subsequently, MALT1 expression, locomotor capability, neural injury, markers for microglia activation and polarization, inflammatory cytokine expressions, and nuclear factor (NF)-κB pathway were detected. SCI rats exhibited higher MALT1 expression, microglia activation and M1 polarization, neuroinflammation, and NF-κB pathway activation, while worse locomotor capacity compared to sham rats (all P < 0.05). In SCI rats, MALT1 knockdown alleviated Basso, Beattie, and Bresnahan score from 10 to 28 days and attenuated HE staining reflected neural injury (all P < 0.05). Besides, MALT1 knockdown declined the number of IBA1+ cells, IBA1+ iNOS+ cells, and IBA1+ CD86+ cells, while enhanced the number of IBA1+ Arg1+ cells and IBA1+ CD206+ cells in SCI rats (all P < 0.05). Meanwhile, MALT1 knockdown declined the expressions of IL-1β, IL-6, and TNF-α in SCI (all P < 0.05), but did not affect IL-10 expression (P > 0.05). Furthermore, MALT1 knockdown suppressed NF-κB pathway activation validated by immunofluorescence staining and western blot assays (all P < 0.05). MALT1 knockdown improves functional recovery, attenuates microglia activation, M1 polarization, and neuroinflammation via inhibiting NF-κB pathway in SCI.

• Authors: Qingping Zhang, Shitao Zhang, Hongquan Chen, Gang Chen, Chunhong Cui, Junxin Zhang, Weiming Wang, Qinghua Zhang, Shiwen Guo
• Journal: Molecular neurobiology (Mol Neurobiol) Vol. 60 Issue 5 Pg. 2632-2643 (May 2023) ISSN: 1559-1182 [Electronic] United States
• PMID: 36692707 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• NF-kappa B
• Malt1 protein, rat

Topics

• Animals
• Rats
• Microglia (metabolism)
• Neuroinflammatory Diseases
• NF-kappa B (metabolism)
• Rats, Sprague-Dawley
• Spinal Cord (pathology)
• Spinal Cord Injuries (pathology)