Anti-inflammatory IL-10 administration rescues depression-associated learning and memory deficits in mice

• Published in: Journal of neuroinflammation Vol. 17; no. 1; p. 246
• Main Authors: Worthen, Ryan J, Garzon Zighelboim, Susan S, Torres Jaramillo, Camila S, Beurel, Eleonore
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 22-08-2020; BioMed Central; BMC
• Subjects: Animals; Behavior; Care and treatment; Cognition & reasoning; Cognitive ability; Complications and side effects; Cytokines; Dendritic spines; Depression (Mood disorder); Depressive Disorder, Major - drug therapy; Development and progression; Disease Models, Animal; Experiments; Genetic aspects; Health aspects; Helplessness, Learned; Hippocampus; Inflammation; Interleukin 10; Interleukin-10 - pharmacology; Interleukin-10 - therapeutic use; Learned helplessness; Learning; Learning - drug effects; Learning and memory; Learning disorders; Male; Memory; Memory - drug effects; Memory Disorders - drug therapy; Mental depression; Mice; Microglia; Mood; Pattern recognition; Psychological aspects; Short term memory; Spatial memory; Treatment Outcome; United States; United States > US; Learning and memory; Learned helplessness; Interleukin-10; Microglia
• ISSN: 1742-2094; 1742-2094
• DOI: 10.1186/s12974-020-01922-1

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.
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.
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 pro-cognitive role for IL-10.
Altogether these data demonstrate the critical role of IL-10 in promoting learning and memory after learned helplessness.