Environmental enrichment enhances autophagy signaling in the rat hippocampus

Takahashi, Tomohisa; Shimizu, Kunio; Shimazaki, Kuniko; Toda, Hiroyuki; Nibuya, Masashi

doi:10.1016/j.brainres.2014.10.026

Cited by 33 publications

(14 citation statements)

References 60 publications

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“…Our results show that EE invokes a significant and consistent alteration in the immune repertoire of male CD1 mice: increasing circulating innate immune cells, enhancing macrophage activity, and altering the host’s gene expression profile to improve bacterial clearance in a model of polymicrobial sepsis. These alterations are evident after only 2 weeks of enrichment, a time frame previously demonstrated to induce significant physiological effects in neurological research ( 25 ) and recently described in our previous study focusing on T cells ( 26 ).…”

Section: Discussionsupporting

confidence: 56%

“…Congruently, administration of the neutrophil attractants CXCL1 and CXCL2 into the peritoneal cavity after inducing polymicrobial sepsis enhances both neutrophil recruitment and clearance of bacteria, as well as improving host survival ( 30 ). Similarly, our recent study ( 25 ) on the influence of the enriched environment on T cell response ex vivo suggest that these cells might contribute to the beneficial effects of this experimental paradigm. Further studies will be needed to dissect the role of the innate and adaptive arms of the immune system in regulating the host immune response.…”

Section: Discussionmentioning

confidence: 60%

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The impact of environmental enrichment on the murine inflammatory immune response

Brod¹,

Gobbetti²,

Gittens³

et al. 2017

JCI Insight

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Living in a mentally and physically stimulating environment has been suggested to have a beneficial effect on the immune response. This study investigates these effects, utilizing a 2-week program of environmental enrichment (EE) and 2 models of acute inflammation: zymosan-induced peritonitis (ZIP) and the cecal ligation and puncture (CLP) model of sepsis. Our results revealed that following exposure to EE, mice possessed a significantly higher circulating neutrophil to lymphocyte ratio compared with control animals. When subject to ZIP, EE animals exhibit enhanced neutrophil and macrophage influx into their peritoneal cavity. Corresponding results were found in CLP, where we observed an improved capacity for enriched animals to clear systemic microbial infection. Ex vivo investigation of leukocyte activity also revealed that macrophages from EE mice presented an enhanced phagocytic capacity. Supporting these findings, microarray analysis of EE animals revealed the increased expression of immunomodulatory genes associated with a heightened and immunoprotective status. Taken together, these results provide potentially novel mechanisms by which EE influences the development and dynamics of the immune response.

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Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 60%

The impact of environmental enrichment on the murine inflammatory immune response

Brod¹,

Gobbetti²,

Gittens³

et al. 2017

JCI Insight

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“…22,30,31 It is now well established that neurotrophins are important mediators of neuronal development, where they modulate dendritic growth and remodeling, membrane receptor trafficking, neurotransmitter release and synapse formation and function. 20,[32][33][34] In our study, neutrophins had a physiological role in the dendritic architecture in the hippocampus. This observation is in line with previous work showing that BDNF regulates dendritic architecture during the early development of hippocampal neurons.…”

Section: Discussionsupporting

confidence: 48%

Neonatal vaccination with bacille Calmette-Guérin promotes the dendritic development of hippocampal neurons

Zhang

Zou

et al. 2015

Human Vaccines & Immunotherapeutics

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y These authors equally contributed to this work.Keywords: dendritic complexity, fractal dimension, neurotrophin, spine, sholl analysis Abbreviations: BCG, Bacillus Calmette-Gu erin; CNS, central nevers system; BDNF, brain derived neurotrophic factor; IGF-1, insulin-like growth factor 1; AMPA, a-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptorDendritic structure is sensitive to changes in the environment during brain development. Accumulating evidence has demonstrated that early immune activation can significantly affect neuronal development. Our study concentrated on the morphological study of neural dendrites and spines in the hippocampal CA1 area using Diolistic labeling with Sholl analysis and fractal analysis. The results revealed that Bacille Calmette-Gu erin (BCG) vaccination enhanced dendritic complexity, as reflected by the increased number of intersections, number of branch points and fractal dimension, and promoted neurite outgrowth. In addition, BCG increased the density and promoted the maturation of dendritic spines. The alterations in dendritic structure and spine morphology were observed at 2 and 4 w, but the differences were more apparent at 4 w than at 2 w. However, no significant difference was observed at 8 w. Furthermore, we observed that BCG increased the expression of hippocampal brain derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1). Hippocampal BDNF/IGF-1 was positively correlated with apical dendritic length, fractal dimension, and spine density. Taken together, we show in this study that neonatal BCG vaccination promotes dendritic development in developing hippocampal CA1 neurons, most likely by increasing the expression of BDNF and IGF-1 in the hippocampus.

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“…Oxidative stress has been shown to cause the accumulation of autophagosomes in different types of somatic cells [7]. Various conditions that induce oxidative stress, such as starvation [8], infection [9], and environmental stress [10], can activate autophagy. Excessive light exposure has been shown to induce autophagy in different types of cells.…”

Section: Introductionmentioning

confidence: 99%

White light emitting diode induces autophagy in hippocampal neuron cells through GSK-3-mediated GR and RORα pathways

Yang

Jia

Sun

et al. 2019

Aging

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Autophagy plays an important role in cell survival under diverse stress conditions. Here, we show that white LED light exposure for 24 h significantly activated autophagy-related genes and increased autophagosome formation in hippocampal neural cells (HT-22). Concurrently, the rhythmic pattern of clock-related gene expression was disrupted, which was associated with augmented expression of SIRT1, AMPK and retinoid-related orphan receptor alpha (RORα). SR1001, a specific inhibitor of RORα, protected the cells from light-induced activation of autophagy. Moreover, light exposure increased glucocorticoid receptor (GR) phosphorylation and nuclear translocation. GR inhibitor RU486 prevented light-induced up-regulation of RORα and the activation of autophagy. These changes were associated with enhanced glycogen synthase kinase-3 (GSK-3) activity and its specific inhibitor CHIR-99021 significantly rescued light-induced autophagy and augmented GR, RORα and autophagy-related proteins. Furthermore, GSK-3 was identified as an upstream regulator of GR/RORα signaling as it was not affected by GR or RORα inhibitors. Taken together, our data demonstrate that GSK-3-mediated GR/RORα signaling pathway is involved in white LED light-induced autophagy in hippocampal neuron cells.

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Environmental enrichment enhances autophagy signaling in the rat hippocampus

Cited by 33 publications

References 60 publications

The impact of environmental enrichment on the murine inflammatory immune response

The impact of environmental enrichment on the murine inflammatory immune response

Neonatal vaccination with bacille Calmette-Guérin promotes the dendritic development of hippocampal neurons

White light emitting diode induces autophagy in hippocampal neuron cells through GSK-3-mediated GR and RORα pathways

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