Anti-inflammatory IL-10 administration rescues depression-associated learning and memory deficits in mice
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(2020) 17:246
RESEARCH
Open Access
Anti-inflammatory IL-10 administration rescues depression-associated learning and memory deficits in mice Ryan J. Worthen1, Susan S. Garzon Zighelboim2, Camila S. Torres Jaramillo2 and Eleonore Beurel1,2*
Abstract Background: Major depressive disorder is a widespread mood disorder. One of the most debilitating symptoms patients often experience is cognitive impairment. Recent findings suggest that inflammation is associated with depression and impaired cognition. Pro-inflammatory cytokines are elevated in the blood of depressed patients and impair learning and memory processes, suggesting that an anti-inflammatory approach might be beneficial for both depression and cognition. Methods: We subjected mice to the learned helplessness paradigm and evaluated novel object recognition and spatial memory. Mice were treated with IL-10 intranasally or/and microglia cells were depleted using PLX5622. Statistical differences were tested using ANOVA or t tests. Results: We first established a mouse model of depression in which learning and memory are impaired. We found that learned helplessness (LH) impairs novel object recognition (NOR) and spatial working memory. LH mice also exhibit reduced hippocampal dendritic spine density and increased microglial activation compared to non-shocked (NS) mice or mice that were subjected to the learned helpless paradigm but did not exhibit learned helplessness (non-learned helpless or NLH). These effects are mediated by microglia, as treatment with PLX5622, which depletes microglia, restores learning and memory and hippocampal dendritic spine density in LH mice. However, PLX5622 also impairs learning and memory and reduces hippocampal dendritic spine density in NLH mice, suggesting that microglia in NLH mice produce molecules that promote learning and memory. We found that microglial interleukin (IL)-10 levels are reduced in LH mice, and IL-10 administration is sufficient to restore NOR, spatial working memory, and hippocampal dendritic spine density in LH mice, and in NLH mice treated with PLX5622 consistent with a procognitive role for IL-10. Conclusions: Altogether these data demonstrate the critical role of IL-10 in promoting learning and memory after learned helplessness. Keywords: Microglia, Learned helplessness, Interleukin-10, Learning and memory
* Correspondence: [email protected] 1 Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Gautier Building room 415, 1011 NW 15th Street, Miami, FL 33136, USA 2 Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Gautier Building room, 4151011 NW 15th Street, Miami, FL 33136, USA © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons
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