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This study was supported by the following: The European Research Council (ERC) (ERC-CoG-2020-101001916 (MLLM) ) ; the Spanish Ministry of Economy and Competitiveness (PID2020-113007RB-I00 (MLLM) ) ; and the Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED, Spain (MLLM) ) . The salary of EPMJ was supported by a 2018 Neuroscience Doctoral fellowship from the Fundacion Tatiana Perez de Guzman and an EMBO Scientific Exchange Grant. The salary of Miguel Flor-Garcia was supported by a "Formacion de Personal Investigador" (FPI) contract, associated with the SAF-2017-82185-R grant (MLLM) , supported by the Spanish Ministry of Economy and Competitiveness (PRE2018-085233) . The salary of JTR was supported by a Doctoral fellowship from the Universidad Autonoma de Madrid (FPI-UAM 2017 program) . The salary of HCR was supported by a fellowship from the Fundacion Universitaria San Pablo CEU-Banco Santander (Santander Research Fellowship: Recruitment of young researchers CEU-Santander) . The authors thank J. Molina- Hernandez for help with the analysis of behavioral tests.

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Azithromycin preserves adult hippocampal neurogenesis and behavior in a mouse model of sepsis

Publicated to:BRAIN BEHAVIOR AND IMMUNITY. 117 135-148 - 2024-01-01 117(), DOI: 10.1016/j.bbi.2024.01.005

Authors: Rodríguez-Moreno, CB; Cañeque-Rufo, HE; Flor-García, M; Terreros-Roncal, J; Moreno-Jiménez, EP; Pallas-Bazarra, N; Bressa, C; Larrosa, M; Cafini, F; Llorens-Martín, M

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Abstract

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.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

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