Cargando…

IL-33 Alleviates Postoperative Cognitive Impairment by Inhibiting Hippocampal Inflammation and Upregulating Excitatory Synaptic Number in Aged Mice

Delayed neurocognitive recovery (dNCR), a postoperative complication that occurs in elderly patients, still lacks effective treatment. Interleukin-33 (IL-33) has been proved to modulate neuroinflammation and synaptic plasticity, among other effects, but the role of IL-33 in dNCR is not clear. We est...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Qi, Zhao, Yuqian, Shi, Chuanchuan, Song, Xuemin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496788/
https://www.ncbi.nlm.nih.gov/pubmed/36138980
http://dx.doi.org/10.3390/brainsci12091244
_version_ 1784794355615137792
author Li, Qi
Zhao, Yuqian
Shi, Chuanchuan
Song, Xuemin
author_facet Li, Qi
Zhao, Yuqian
Shi, Chuanchuan
Song, Xuemin
author_sort Li, Qi
collection PubMed
description Delayed neurocognitive recovery (dNCR), a postoperative complication that occurs in elderly patients, still lacks effective treatment. Interleukin-33 (IL-33) has been proved to modulate neuroinflammation and synaptic plasticity, among other effects, but the role of IL-33 in dNCR is not clear. We established a dNCR model in aged mice by laparotomy under sevoflurane anesthesia. Cognition was evaluated by Morris water maze (MWM) and fear conditioning test (FCT). Immunofluorescence was used to detect the density of IL-33 and glial fibrillary acidic protein (GFAP) co-localization, ionized calcium-binding adapter molecule 1, vesicular glutamate transporter 1 (vGlut1) and postsynaptic density protein-95 (PSD95) co-localization in the hippocampus. IL-33, GFAP, vGlut1 and PSD95 were tested by Western blotting. Enzyme-linked immunosorbent assay was used to detect the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and IL-10. Surgery/anesthesia reduced the level of IL-33 in the hippocampus. Intraperitoneal injection of 200 ng IL-33 per mouse significantly decreased the latency to the platform and increased the number of platform crossings and the target quadrant dwell time in MWM, while increasing the freezing time in the context test of FCT. Furthermore, IL-33 inhibited microglial activation and the release of TNF-α and IL-1β while upregulating the markers of excitatory synapses vGlut1 and PSD95. Our findings indicated that IL-33 improved cognition by inhibiting the hippocampal inflammatory response and upregulating the number of excitatory synapses. Therefore, IL-33 is a potential drug for the treatment of dNCR.
format Online
Article
Text
id pubmed-9496788
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-94967882022-09-23 IL-33 Alleviates Postoperative Cognitive Impairment by Inhibiting Hippocampal Inflammation and Upregulating Excitatory Synaptic Number in Aged Mice Li, Qi Zhao, Yuqian Shi, Chuanchuan Song, Xuemin Brain Sci Article Delayed neurocognitive recovery (dNCR), a postoperative complication that occurs in elderly patients, still lacks effective treatment. Interleukin-33 (IL-33) has been proved to modulate neuroinflammation and synaptic plasticity, among other effects, but the role of IL-33 in dNCR is not clear. We established a dNCR model in aged mice by laparotomy under sevoflurane anesthesia. Cognition was evaluated by Morris water maze (MWM) and fear conditioning test (FCT). Immunofluorescence was used to detect the density of IL-33 and glial fibrillary acidic protein (GFAP) co-localization, ionized calcium-binding adapter molecule 1, vesicular glutamate transporter 1 (vGlut1) and postsynaptic density protein-95 (PSD95) co-localization in the hippocampus. IL-33, GFAP, vGlut1 and PSD95 were tested by Western blotting. Enzyme-linked immunosorbent assay was used to detect the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and IL-10. Surgery/anesthesia reduced the level of IL-33 in the hippocampus. Intraperitoneal injection of 200 ng IL-33 per mouse significantly decreased the latency to the platform and increased the number of platform crossings and the target quadrant dwell time in MWM, while increasing the freezing time in the context test of FCT. Furthermore, IL-33 inhibited microglial activation and the release of TNF-α and IL-1β while upregulating the markers of excitatory synapses vGlut1 and PSD95. Our findings indicated that IL-33 improved cognition by inhibiting the hippocampal inflammatory response and upregulating the number of excitatory synapses. Therefore, IL-33 is a potential drug for the treatment of dNCR. MDPI 2022-09-14 /pmc/articles/PMC9496788/ /pubmed/36138980 http://dx.doi.org/10.3390/brainsci12091244 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Li, Qi
Zhao, Yuqian
Shi, Chuanchuan
Song, Xuemin
IL-33 Alleviates Postoperative Cognitive Impairment by Inhibiting Hippocampal Inflammation and Upregulating Excitatory Synaptic Number in Aged Mice
title IL-33 Alleviates Postoperative Cognitive Impairment by Inhibiting Hippocampal Inflammation and Upregulating Excitatory Synaptic Number in Aged Mice
title_full IL-33 Alleviates Postoperative Cognitive Impairment by Inhibiting Hippocampal Inflammation and Upregulating Excitatory Synaptic Number in Aged Mice
title_fullStr IL-33 Alleviates Postoperative Cognitive Impairment by Inhibiting Hippocampal Inflammation and Upregulating Excitatory Synaptic Number in Aged Mice
title_full_unstemmed IL-33 Alleviates Postoperative Cognitive Impairment by Inhibiting Hippocampal Inflammation and Upregulating Excitatory Synaptic Number in Aged Mice
title_short IL-33 Alleviates Postoperative Cognitive Impairment by Inhibiting Hippocampal Inflammation and Upregulating Excitatory Synaptic Number in Aged Mice
title_sort il-33 alleviates postoperative cognitive impairment by inhibiting hippocampal inflammation and upregulating excitatory synaptic number in aged mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496788/
https://www.ncbi.nlm.nih.gov/pubmed/36138980
http://dx.doi.org/10.3390/brainsci12091244
work_keys_str_mv AT liqi il33alleviatespostoperativecognitiveimpairmentbyinhibitinghippocampalinflammationandupregulatingexcitatorysynapticnumberinagedmice
AT zhaoyuqian il33alleviatespostoperativecognitiveimpairmentbyinhibitinghippocampalinflammationandupregulatingexcitatorysynapticnumberinagedmice
AT shichuanchuan il33alleviatespostoperativecognitiveimpairmentbyinhibitinghippocampalinflammationandupregulatingexcitatorysynapticnumberinagedmice
AT songxuemin il33alleviatespostoperativecognitiveimpairmentbyinhibitinghippocampalinflammationandupregulatingexcitatorysynapticnumberinagedmice