Azithromycin preserves adult hippocampal neurogenesis and behavior in a mouse model of sepsis
Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved..
The mammalian hippocampus can generate new neurons throughout life. Known as adult hippocampal neurogenesis (AHN), this process participates in learning, memory, mood regulation, and forgetting. The continuous incorporation of new neurons enhances the plasticity of the hippocampus and contributes to the cognitive reserve in aged individuals. However, the integrity of AHN is targeted by numerous pathological conditions, including neurodegenerative diseases and sustained inflammation. In this regard, the latter causes cognitive decline, mood alterations, and multiple AHN impairments. In fact, the systemic administration of Lipopolysaccharide (LPS) from E. coli to mice (a model of sepsis) triggers depression-like behavior, impairs pattern separation, and decreases the survival, maturation, and synaptic integration of adult-born hippocampal dentate granule cells. Here we tested the capacity of the macrolide antibiotic azithromycin to neutralize the deleterious consequences of LPS administration in female C57BL6J mice. This antibiotic exerted potent neuroprotective effects. It reversed the increased immobility time during the Porsolt test, hippocampal secretion of pro-inflammatory cytokines, and AHN impairments. Moreover, azithromycin promoted the synaptic integration of adult-born neurons and functionally remodeled the gut microbiome. Therefore, our data point to azithromycin as a clinically relevant drug with the putative capacity to ameliorate the negative consequences of chronic inflammation by modulating AHN and hippocampal-related behaviors.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:117 |
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| Enthalten in: |
Brain, behavior, and immunity - 117(2024) vom: 29. März, Seite 135-148 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Rodríguez-Moreno, Carla B [VerfasserIn] |
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| Links: |
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| Themen: |
83905-01-5 |
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| Anmerkungen: |
Date Completed 04.03.2024 Date Revised 07.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bbi.2024.01.005 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 245 | 1 | 0 | |a Azithromycin preserves adult hippocampal neurogenesis and behavior in a mouse model of sepsis |
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| 520 | |a Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a The mammalian hippocampus can generate new neurons throughout life. Known as adult hippocampal neurogenesis (AHN), this process participates in learning, memory, mood regulation, and forgetting. The continuous incorporation of new neurons enhances the plasticity of the hippocampus and contributes to the cognitive reserve in aged individuals. However, the integrity of AHN is targeted by numerous pathological conditions, including neurodegenerative diseases and sustained inflammation. In this regard, the latter causes cognitive decline, mood alterations, and multiple AHN impairments. In fact, the systemic administration of Lipopolysaccharide (LPS) from E. coli to mice (a model of sepsis) triggers depression-like behavior, impairs pattern separation, and decreases the survival, maturation, and synaptic integration of adult-born hippocampal dentate granule cells. Here we tested the capacity of the macrolide antibiotic azithromycin to neutralize the deleterious consequences of LPS administration in female C57BL6J mice. This antibiotic exerted potent neuroprotective effects. It reversed the increased immobility time during the Porsolt test, hippocampal secretion of pro-inflammatory cytokines, and AHN impairments. Moreover, azithromycin promoted the synaptic integration of adult-born neurons and functionally remodeled the gut microbiome. Therefore, our data point to azithromycin as a clinically relevant drug with the putative capacity to ameliorate the negative consequences of chronic inflammation by modulating AHN and hippocampal-related behaviors | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Adult hippocampal neurogenesis | |
| 650 | 4 | |a Azithromycin | |
| 650 | 4 | |a Cytokines | |
| 650 | 4 | |a Gut microbiome | |
| 650 | 4 | |a LPS | |
| 650 | 4 | |a Retrovirus | |
| 650 | 7 | |a Azithromycin |2 NLM | |
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| 650 | 7 | |a Lipopolysaccharides |2 NLM | |
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| 700 | 1 | |a Cañeque-Rufo, Héctor |e verfasserin |4 aut | |
| 700 | 1 | |a Flor-García, Miguel |e verfasserin |4 aut | |
| 700 | 1 | |a Terreros-Roncal, Julia |e verfasserin |4 aut | |
| 700 | 1 | |a Moreno-Jiménez, Elena P |e verfasserin |4 aut | |
| 700 | 1 | |a Pallas-Bazarra, Noemí |e verfasserin |4 aut | |
| 700 | 1 | |a Bressa, Carlo |e verfasserin |4 aut | |
| 700 | 1 | |a Larrosa, Mar |e verfasserin |4 aut | |
| 700 | 1 | |a Cafini, Fabio |e verfasserin |4 aut | |
| 700 | 1 | |a Llorens-Martín, María |e verfasserin |4 aut | |
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