Leptin Attenuates Fear Memory by Inhibiting Astrocytic NLRP3 Inflammasome in Post-traumatic Stress Disorder Model.
Astrocytes
Leptin
NLRP3 inflammasome
Post-traumatic stress disorder
STAT3
Journal
Neurochemical research
ISSN: 1573-6903
Titre abrégé: Neurochem Res
Pays: United States
ID NLM: 7613461
Informations de publication
Date de publication:
Apr 2023
Apr 2023
Historique:
received:
27
05
2022
accepted:
08
06
2022
pubmed:
25
6
2022
medline:
24
3
2023
entrez:
24
6
2022
Statut:
ppublish
Résumé
Accumulating evidence suggests that the activation of nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome contributes to the pathophysiology of post-traumatic stress disorder (PTSD). Astrocytes, the homeostatic cells of the central nervous system are intimately involved into pathophysiology of various mental disorders including PTSD. We demonstrated previously that leptin exerts neuroprotection and ameliorates chronic sleep deprivation-induced depressive-like behaviours. Here, we extended the study of therapeutic effects of leptin to PTSD model mice. We discovered that PTSD is associated with significant activation of NLRP3 inflammasome in astrocytes sorted from GFAP-GFP transgenic mice, while administration of leptin markedly suppressed the activation of astrocytic NLRP3 inflammasome. Leptin effectively improved PTSD-associated behavioural alterations including fear memory, cognitive impairments, and depressive-like behaviours. Therapeutic effects of leptin were mediated by the signal transducer and activator of transcription 3 (STAT3) in astrocytes. In addition, the PTSD-related activation of NLRP3 inflammasome impairs astrocytic mitochondria suppressing ATP synthesis and leading to an increased ROS production. Leptin reversed mitochondrial inhibition by stimulating STAT3 in astrocytes. We propose leptin as a novel candidate for the pharmacological treatment of PTSD.
Identifiants
pubmed: 35750877
doi: 10.1007/s11064-022-03655-4
pii: 10.1007/s11064-022-03655-4
doi:
Substances chimiques
Inflammasomes
0
NLR Family, Pyrin Domain-Containing 3 Protein
0
Leptin
0
Nlrp3 protein, mouse
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1180-1190Subventions
Organisme : National Natural Science Foundation of China
ID : 81871852
Organisme : Shenyang Science and Technology Innovation Talents Project
ID : RC210251
Organisme : Wellcome Trust
ID : 202078
Pays : United Kingdom
Organisme : 'ChunHui' Program of Education Ministry
ID : 2020703
Organisme : Wellcome Trust
ID : 202078
Pays : United Kingdom
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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