Chronic IL-10 overproduction disrupts microglia-neuron dialogue similar to aging, resulting in impaired hippocampal neurogenesis and spatial memory
Sanchez-Molina, Paula (Universitat Autònoma de Barcelona. Institut de Neurociències)
Almolda Ardid, Beatriz (Universitat Autònoma de Barcelona. Institut de Neurociències)
Gimenez-Llort, Lydia (Universitat Autònoma de Barcelona. Institut de Neurociències)
González, Berta (Universitat Autònoma de Barcelona. Institut de Neurociències)
Castellano López, Bernardo (Universitat Autònoma de Barcelona. Institut de Neurociències)

Date:	2022
Abstract:	The subgranular zone of the dentate gyrus is an adult neurogenic niche where new neurons are continuously generated. A dramatic hippocampal neurogenesis decline occurs with increasing age, contributing to cognitive deficits. The process of neurogenesis is intimately regulated by the microenvironment, with inflammation being considered a strong negative factor for this process. Thus, we hypothesize that the reduction of new neurons in the aged brain could be attributed to the age-related microenvironmental changes towards a pro-inflammatory status. In this work, we evaluated whether an anti-inflammatory microenvironment could counteract the negative effect of age on promoting new hippocampal neurons. Surprisingly, our results show that transgenic animals chronically overexpressing IL-10 by astrocytes present a decreased hippocampal neurogenesis in adulthood. This results from an impairment in the survival of neural newborn cells without differences in cell proliferation. In parallel, hippocampal-dependent spatial learning and memory processes were affected by IL-10 overproduction as assessed by the Morris water maze test. Microglial cells, which are key players in the neurogenesis process, presented a different phenotype in transgenic animals characterized by high activation together with alterations in receptors involved in neuronal communication, such as CD200R and CX3CR1. Interestingly, the changes described in adult transgenic animals were similar to those observed by the effect of normal aging. Thus, our data suggest that chronic IL-10 overproduction mimics the physiological age-related disruption of the microglia-neuron dialogue, resulting in hippocampal neurogenesis decrease and spatial memory impairment.
Grants:	Ministerio de Economía y Competitividad BFU2014-55459 Ministerio de Economía y Competitividad BFU2017-87843-R
Note:	Altres ajuts: acords transformatius de la UAB
Note:	This work was supported by the Spanish Ministry of Economy and Business (BFU2014-55459 and BFU2017-87843-R).
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Neurogenesis ; IL-10 ; Aging ; Microglia ; Memory ; CX3CR1 ; CD200R ; Hippocampus
Published in:	Brain, Behavior, and Immunity, Vol. 101 (march 2022) , p. 231-245, ISSN 1090-2139

DOI: 10.1016/j.bbi.2021.12.026
PMID: 34990747

15 p, 3.8 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles