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

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.

Memory Impairment Related to NLRP3 Inflammasome Activation and TRPC5 Decrease in Hippocampal Excitatory Synapses in Microglia Knockout IL-10 Mice

“…This result is similar to the results of other relevant studies, in which IL-10 tm1/tm1 male mice with a low expression of IL-10 exhibited defective learning and memory behaviors in the MWM test [7]. A recent study showed that IL-10 produced from microglial cells in non-learned helpless mice is necessary to maintain learning and memory [19].Intranasal administration of IL-10 increased dendritic spine density by 2.0-and 4.3-fold in the dentate gyrus of non-learned helpless and learned helpless mice [19].…”

Dual Anti-Malarial and GSK3β-Mediated Cytokine-Modulating Activities of Quercetin Are Requisite of Its Potential as a Plant-Derived Therapeutic in Malaria

“…Nevertheless, GSK3 may be one of the plausible targets to be exploited in adjunctive therapy to overcome neurological deficits. Recently, Worthen et al [ 61 ] demonstrated that anti-inflammatory IL-10 administration rescues depression-associated learning and memory deficits in mice. As mentioned earlier, Dai et al [ 57 ] reported that LiCl treatment restored long-term neurocognitive function in experimental cerebral malaria.…”

Anti-Inflammatory Effects of Asian Fawn Lily (Erythronium japonicum) Extract on Lipopolysaccharide-Induced Depressive-Like Behavior in Mice

“…Previous in vivo studies have reported that inhibition of pro-inflammatory cytokines alleviated depressive symptoms [ 33 , 34 , 35 ]. Furthermore, depressive-like behaviors were attenuated by the administration of IL-10 in mice [ 36 ]. These data demonstrate that the regulation of cytokine expression can attenuate depressive symptoms.…”