Nucleophosmin 1 overexpression enhances neuroprotection by attenuating cellular stress in traumatic brain injury.

Cellular stress Mitochondrial damage Nucleophosmin 1 P53 Traumatic brain injury

Journal

Experimental neurology
ISSN: 1090-2430
Titre abrégé: Exp Neurol
Pays: United States
ID NLM: 0370712

Informations de publication

Date de publication:
18 Oct 2024
Historique:
received: 19 02 2024
revised: 08 06 2024
accepted: 17 10 2024
medline: 21 10 2024
pubmed: 21 10 2024
entrez: 20 10 2024
Statut: aheadofprint

Résumé

Traumatic Brain Injury (TBI) is a multifaceted injury that can cause a wide range of symptoms and impairments, leading to significant effects on brain function. Nucleophosmin 1 (NPM1), a versatile phosphoprotein located in the nucleolus, is being recognized as a possible controller of cellular stress reactions and could be important in reducing neuro dysfunction caused by TBI. However the critical roles of NPM1 in cellular stress in TBI remains unclear. We employed a control cortical impact mouse model and a scratch-induced primary neuronal culture model. Hematoxylin and eosin staining was used to evaluate tissue damage and cellular changes, with NPM1 expression in the cortical area assessed through immunofluorescence staining and Western blot analysis. Neuronal morphology was assessed using Nissl staining. Behavioral assessments were performed to evaluate the impact of NPM1 overexpression on neurobehavioral results in TBI mice. Mitochondrial function was assessed using an Extracellular Flux Analyzer. Following TBI, an increase in NPM1 expression was observed, with a peak at 72 h post-injury. Increased levels of NPM1 resulted in decreased neuronal cell death, as shown by Nissl staining, and lower levels of Caspase 8, APE1, H2AX, and 8-OHDG expression, indicating a reduction in DNA damage. NPM1 overexpression also resulted in improved neurobehavioral outcomes, characterized by decreased neurological deficits and enhanced motor function post-TBI. Additionally, in vitro, scratch-induction experiments revealed that NPM1 overexpression mitigated mitochondrial damage, as evidenced by the downregulation of P53, BCL2, and Cyto C expression levels and improvements in mitochondrial respiratory function. These findings suggest NPM1 as a promising target for developing interventions to alleviate TBI-related cellular stress and promote neuronal survival.

Sections du résumé

BACKGROUND BACKGROUND
Traumatic Brain Injury (TBI) is a multifaceted injury that can cause a wide range of symptoms and impairments, leading to significant effects on brain function. Nucleophosmin 1 (NPM1), a versatile phosphoprotein located in the nucleolus, is being recognized as a possible controller of cellular stress reactions and could be important in reducing neuro dysfunction caused by TBI. However the critical roles of NPM1 in cellular stress in TBI remains unclear.
METHODS METHODS
We employed a control cortical impact mouse model and a scratch-induced primary neuronal culture model. Hematoxylin and eosin staining was used to evaluate tissue damage and cellular changes, with NPM1 expression in the cortical area assessed through immunofluorescence staining and Western blot analysis. Neuronal morphology was assessed using Nissl staining. Behavioral assessments were performed to evaluate the impact of NPM1 overexpression on neurobehavioral results in TBI mice. Mitochondrial function was assessed using an Extracellular Flux Analyzer.
RESULTS RESULTS
Following TBI, an increase in NPM1 expression was observed, with a peak at 72 h post-injury. Increased levels of NPM1 resulted in decreased neuronal cell death, as shown by Nissl staining, and lower levels of Caspase 8, APE1, H2AX, and 8-OHDG expression, indicating a reduction in DNA damage. NPM1 overexpression also resulted in improved neurobehavioral outcomes, characterized by decreased neurological deficits and enhanced motor function post-TBI. Additionally, in vitro, scratch-induction experiments revealed that NPM1 overexpression mitigated mitochondrial damage, as evidenced by the downregulation of P53, BCL2, and Cyto C expression levels and improvements in mitochondrial respiratory function.
CONCLUSION CONCLUSIONS
These findings suggest NPM1 as a promising target for developing interventions to alleviate TBI-related cellular stress and promote neuronal survival.

Identifiants

DOI: 10.1016/j.expneurol.2024.115019 PMID: 39428041
pubmed: 39428041
pii: S0014-4886(24)00345-5
doi: 10.1016/j.expneurol.2024.115019
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

115019

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.

Auteurs

Jiashuo Zhao (J)

Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province 215006, China.

Weixin Xing (W)

Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province 215006, China.

Chengyuan Ji (C)

Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province 215006, China.

Hongwei Hu (H)

Department of Neurosurgery, Changzhou Jintan First People's Hospital Affiliated to Jiangsu University, 500 Jintan Avenue, Jintan 210036, China.

Yuanqing Zhang (Y)

Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province 215006, China.

Zongqi Wang (Z)

Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province 215006, China. Electronic address: wangzognqi1992@suda.edu.cn.

Jiangang Liu (J)

Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province 215006, China. Electronic address: liujiangang@suda.edu.cn.

Classifications MeSH