Mitochondrial modulation treating postoperative cognitive dysfunction neuroprotection via DRP1 inhibition by Mdivi1.

Dynamins / metabolism Animals Mice Mitochondria / metabolism Mitochondrial Dynamics / drug effects Quinazolinones / pharmacology Postoperative Cognitive Complications / metabolism Male Reactive Oxygen Species / metabolism Microglia / metabolism Disease Models, Animal Neuroprotection / drug effects Membrane Potential, Mitochondrial / drug effects Mice, Inbred C57BL Hippocampus / metabolism Neuronal Plasticity / drug effects NLR Family, Pyrin Domain-Containing 3 Protein / metabolism Neuroprotective Agents / pharmacology
DRP1 NLRP3 Neuroinflammation POCD

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
30 10 2024
Historique:
received: 11 05 2024
accepted: 07 10 2024
medline: 31 10 2024
pubmed: 31 10 2024
entrez: 31 10 2024
Statut: epublish

Résumé

This study investigated the role of mitochondrial dynamics in postoperative cognitive dysfunction (POCD) and assessed the therapeutic potential of mitochondrial modulation, particularly through the inhibition of dynamin-related protein 1 (DRP1) with Mdivi-1. Our findings indicated that DRP1 inhibition substantially mitigated neuroinflammation mediated by microglial cells, contributing to improved cognitive function in POCD models. The administration of Mdivi-1 led to a notable decrease in mitochondrial fission, reduced reactive oxygen species (ROS) production, and stabilization of mitochondrial membrane potential, all of which correlate with diminished neuroinflammation, as evidenced by lower NOD-like receptor family pyrin domain containing 3 (NLRP3)/ interleukin-1β (IL-1β) expression in microglial cells. Importantly, Mdivi-1 treatment was also found to enhance synaptic plasticity, increasing synaptic spine density in the hippocampal region of POCD mice. This improvement in mitochondrial health and synaptic integrity was paralleled by enhanced cognitive performance, as demonstrated in Y-maze tests. These results underscored the critical role of mitochondrial dynamics in the pathophysiology of POCD and suggested that targeting mitochondrial dysfunction, specifically through DRP1 inhibition, could be an effective approach for POCD treatment.

Identifiants

DOI: 10.1038/s41598-024-75548-1 PMID: 39478015
pubmed: 39478015
doi: 10.1038/s41598-024-75548-1
pii: 10.1038/s41598-024-75548-1
doi:

Substances chimiques

Dynamins EC 3.6.5.5
3-(2,4-dichloro-5-methoxyphenyl)-2-sulfanyl-4(3H)-quinazolinone 0
Dnm1l protein, mouse EC 3.6.5.5
Quinazolinones 0
Reactive Oxygen Species 0
NLR Family, Pyrin Domain-Containing 3 Protein 0
Neuroprotective Agents 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

26155

Subventions

Organisme : National Natural Science Foundation of China
ID : 81971290

Informations de copyright

© 2024. The Author(s).

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Auteurs

Jun Ying (J)

Department of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Department of Anesthesiology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.

Xiaobing Deng (X)

Department of Anesthesiology, Lushan Rehabilitation and Recuperation Center, PLA Joint Logistics Support Force, Jiujiang, China.

Ruini Du (R)

Department of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Qiyang Ding (Q)

Department of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Hao Tian (H)

Department of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Yue Lin (Y)

Department of Anesthesiology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.

Bin Zhou (B)

Department of Anesthesiology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.

Wei Gao (W)

Department of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. gaowei2906@xjtufh.edu.cn.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines du transport vésiculaire › Dynamines › Mitochondrial modulation treating...
questionsmedicales.fr › Eucaryotes › Animaux › Mitochondrial modulation treating...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Mitochondrial modulation treating...
questionsmedicales.fr › Cellules › Structures cellulaires › Fractions subcellulaires › Mitochondries › Mitochondrial modulation treating...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Renouvellement des mitochondries › Dynamique mitochondriale › Mitochondrial modulation treating...
questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Quinazolines › Quinazolinones › Mitochondrial modulation treating...
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Troubles de la cognition › Dysfonctionnement cognitif › Complications post-opératoires cognitives › Mitochondrial modulation treating...
questionsmedicales.fr › Produits chimiques inorganiques › Composés de l'oxygène › Espèces réactives de l'oxygène › Mitochondrial modulation treating...
questionsmedicales.fr › Cellules › Névroglie › Microglie › Mitochondrial modulation treating...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Mitochondrial modulation treating...
questionsmedicales.fr › Phénomènes physiologiques de l'appareil locomoteur et du système nerveux › Phénomènes physiologiques du système nerveux › Neuroprotection › Mitochondrial modulation treating...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes électrophysiologiques › Potentiel de membrane mitochondriale › Mitochondrial modulation treating...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Mitochondrial modulation treating...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Prosencéphale › Télencéphale › Cerveau › Cortex cérébral › Hippocampe › Mitochondrial modulation treating...
questionsmedicales.fr › Phénomènes physiologiques de l'appareil locomoteur et du système nerveux › Phénomènes physiologiques du système nerveux › Plasticité neuronale › Mitochondrial modulation treating...
questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Protéines NLR › Protéine-3 de la famille des NLR contenant un domaine pyrine › Mitochondrial modulation treating...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Agents du système nerveux central › Neuroprotecteurs › Mitochondrial modulation treating...