The impact of environmental enrichment on the murine inflammatory immune response

Brod, Samuel; Gobbetti, Thomas; Gittens, Beatrice; Ono, M.; Perretti, Mauro; D’Acquisto, Fulvio

doi:10.1172/jci.insight.90723

Cited by 37 publications

(34 citation statements)

References 57 publications

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“…ArtinM capture by the lymphatic system makes possible the lectin to pass through the appropriate circuit for exerting its immunomodulatory effect, while preserving its bioavailability as an immunomodulatory agent and reproducing advantages that were already reported for vaccines and adjuvants [ 36 , 42 , 43 ]. Recently, Broad et al demonstrated that mice maintained in an enriched environment (EE) favors the modulation of their immune response, determined by infecting the mice and verifying that the inflammatory response favors the resolution of the systemic infection [ 44 ]. The immunomodulation induced by EE and ArtinM are similar because both are imperceptible in naïve mice but notable in infected animals [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, Broad et al demonstrated that mice maintained in an enriched environment (EE) favors the modulation of their immune response, determined by infecting the mice and verifying that the inflammatory response favors the resolution of the systemic infection [ 44 ]. The immunomodulation induced by EE and ArtinM are similar because both are imperceptible in naïve mice but notable in infected animals [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

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Systemic effects in naïve mice injected with immunomodulatory lectin ArtinM

et al. 2017

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Toll-like receptors (TLR) contain N-glycans, which are important glycotargets for plant lectins, to induce immunomodulation. The lectin ArtinM obtained from Artocarpus heterophyllus interacts with TLR2 N-glycans to stimulate IL-12 production by antigen-presenting cells and to drive the immune response toward the Th1 axis, conferring resistance against intracellular pathogens. This immunomodulatory effect was demonstrated by subcutaneously injecting (s.c.) ArtinM (0.5 μg) in infected mice. In this study, we evaluated the systemic implications of ArtinM administration in naïve BALB/c mice. The mice were s.c. injected twice (7 days interval) with ArtinM (0.5, 1.0, 2.5, or 5.0 μg), LPS (positive control), or PBS (negative control) and euthanized after three days. None of the ArtinM-injected mice exhibited change in body weight, whereas the relative mass of the heart and lungs diminished in mice injected with the highest ArtinM dose (5.0 μg). Few and discrete inflammatory foci were detected in the heart, lung, and liver of mice receiving ArtinM at doses ≥2.5 μg. Moreover, the highest dose of ArtinM was associated with increased serum levels of creatine kinase MB isoenzyme (CK-MB) and globulins as well as an augmented presence of neutrophils in the heart and lung. IL-12, IFN-γ, TNF-α, and IL-10 measurements in the liver, kidney, spleen, heart, and lung homogenates revealed decreased IL-10 level in the heart and lung of mice injected with 5.0 μg ArtinM. We also found an augmented frequency of T helper and B cells in the spleen of all ArtinM-injected naïve mice, whereas the relative expressions of T-bet, GATA-3, and ROR-γt were similar to those in PBS-injected animals. Our study demonstrates that s.c. injection of high doses of ArtinM in naïve mice promotes mild inflammatory lesions and that a low immunomodulatory dose is innocuous to naïve mice.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Systemic effects in naïve mice injected with immunomodulatory lectin ArtinM

et al. 2017

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“…This central inflammation is characterized by an increase in the hippocampal expression of proinflammatory cytokines (including IL-1β, IL-6, and TNF-α) and a decrease in the expression of neurotrophic (BDNF and NGF) and neuromodulatory factors. EE attenuates hippocampal neuroinflammation and therefore prevents the plasticity alteration [59][60][61].…”

Section: Effect Of Ee On Hippocampal Plasticitymentioning

confidence: 99%

How Does an Enriched Environment Impact Hippocampus Brain Plasticity?

Zarif¹,

Nicolas²,

Petit-Paitel³

et al. 2018

The Hippocampus - Plasticity and Functions

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Brain plasticity is profoundly impacted by one's living environment. The hippocampus, involved in learning and memory, is highly susceptible to plasticity. Raising rodents in an "enriched environment" (EE) increases learning and memorization aptitudes and decreases the anxiety of the animals. EE consists of a combination of running wheels for voluntary physical exercise, complex inanimate toys, nests, mazes, etc. all of which favor sensory stimulations and social enrichment. EE housing concomitantly increases proliferation and survival of neurons and glia in the dentate gyrus of the hippocampus, induces changes in neuronal morphology, modifies synaptic plasticity, and favors angiogenesis. The mechanisms underlying the effects of EE on plasticity, which have recently been investigated are reviewed here, including the role of glia, the involvement of molecular factors including neurotransmitters (glutamate), neurotrophic factors (BDNF), adipokines (leptin and adiponectin), chemokines, cytokines, and hormones (corticosteroid and thyroid hormones), and at a higher level, the various systems involved (neural networks and hormonal systems). We emphasize recent findings that demonstrate the major role of the immune system in modulating EE-induced changes to hippocampal plasticity. This process involves a variety of immune cells (including macrophages, microglia, natural killer, B-cells, and T-cells), although the mechanisms are yet to be fully elucidated.

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“…Experimentally induced sickness, through the injection of bacterial toxins, has been shown to diminish structural plasticity, including adult neurogenesis in the hippocampus (Bastos, Moriya, Inui, Katura, & Nakahata, 2008; Fujioka & Akema, 2010), as well as to impair cognitive function (Lee et al, 2008; Valero, Mastrella, Neiva, Sánchez, & Malva, 2014) and increase anxiety-like behavior (Bassi et al, 2012; Savignac et al, 2016). Enriched environment living has been shown to have impacts on the immune system by enhancing its ability to fight infection (Brod et al, 2017) and tumors (Garofalo et al, 2015), as well as diminishing inflammatory effects in certain brain regions (Mlynarik, Johansson, & Jezova, 2004; Williamson et al, 2012). Taken together, these findings suggest complex relationships among enrichment, stress, infection, and hippocampal structure and function, yet questions remain.…”

Section: Introductionmentioning

confidence: 99%

The effects of living in an outdoor enclosure on hippocampal plasticity and anxiety‐like behavior in response to nematode infection

et al. 2018

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The hippocampus of rodents undergoes structural remodeling throughout adulthood, including the addition of new neurons. Adult neurogenesis is sensitive to environmental enrichment and stress. Microglia, the brain’s resident immune cells, are involved in adult neurogenesis by engulfing dying new neurons. While previous studies using laboratory environmental enrichment have investigated alterations in brain structure and function, they do not provide an adequate reflection of living in the wild, in which stress and environmental instability are common. Here, we compared mice living in standard laboratory settings to mice living in outdoor enclosures to assess the complex interactions among environment, gut infection, and hippocampal plasticity. We infected mice with parasitic worms and studied their effects on adult neurogenesis, microglia, and functions associated with the hippocampus, including cognition and anxiety regulation. We found an increase in immature neuron numbers of mice living in outdoor enclosures regardless of infection. While outdoor living prevented increases in microglial reactivity induced by infection in both the dorsal and ventral hippocampus, outdoor mice with infection had fewer microglia and microglial processes in the ventral hippocampus. We observed no differences in cognitive performance on the hippocampus-dependent object location task between infected and uninfected mice living in either setting. However, we found that infection caused an increase in anxiety-like behavior in the open field test but only in outdoor mice. These findings suggest that living conditions, as well as gut infection, interact to produce complex effects on brain structure and function.

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The impact of environmental enrichment on the murine inflammatory immune response

Cited by 37 publications

References 57 publications

Systemic effects in naïve mice injected with immunomodulatory lectin ArtinM

Systemic effects in naïve mice injected with immunomodulatory lectin ArtinM

How Does an Enriched Environment Impact Hippocampus Brain Plasticity?

The effects of living in an outdoor enclosure on hippocampal plasticity and anxiety‐like behavior in response to nematode infection

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