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Cellular and molecular mechanisms of immunomodulation in the brain through environmental enrichment
Open accessAbstract
Recent studies on environmental enrichment (EE) have shown cytokines, cellular immune components [e.g., T lymphocytes, natural killer (NK) cells], and glial cells in causal relationship to EE in bringing out changes to neurobiology and behavior. The purpose of this review is to evaluate these neuroimmune mechanisms associated with neurobiological and behavioral changes in response to different EE methods. We systematically reviewed common research databases. After applying all inclusion and exclusion criteria, 328 articles remained for this review. Physical exercise (PE), a form of EE, elicits anti-inflammatory and neuromodulatory effects through interaction with several immune pathways including interleukin (IL)-6 secretion from muscle fibers, reduced expression of Toll-like receptors on monocytes and macrophages, reduced secretion of adipokines, modulation of hippocampal T cells, priming of microglia, and upregulation of mitogen-activated protein kinase phosphatase-1 in central nervous system. In contrast, immunomodulatory roles of other enrichment methods are not studied extensively. Nonetheless, studies showing reduction in the expression of IL-1β and tumor necrosis factor-α in response to enrichment with novel objects and accessories suggest anti-inflammatory effects of novel environment. Likewise, social enrichment, though considered a necessity for healthy behavior, results in immunosuppression in socially defeated animals. This has been attributed to reduction in T lymphocytes, NK cells and IL-10 in subordinate animals. EE through sensory stimuli has been investigated to a lesser extent and the effect on immune factors has not been evaluated yet. Discovery of this multidimensional relationship between immune system, brain functioning, and EE has paved a way toward formulating environ-immuno therapies for treating psychiatric illnesses with minimal use of pharmacotherapy. While the immunomodulatory role of PE has been evaluated extensively, more research is required to investigate neuroimmune changes associated with other enrichment methods.
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“Among those pathways, researchers showed that the inflammasome plays a role in depressive- and anxiety-like behaviors, and locomotor activity (57).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [57]
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“…the cage walls/grid could be an example of resistance exercise which is seen even in the absence of a running wheel in cages and has been Frontiers in Cellular Neuroscience www.frontiersin.org April 2014 | Volume 8 | Article 97 | 19 reported to improve spatial memory (Cassilhas et al., 2012).”
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Metadata
- Authors
- Singhal, G., Jaehne, E. J., Corrigan, F., & Baune, B. T.
- Affiliations
- The University of Adelaide (AU)
- Corresponding author
- Baune, Bernhard T.
- Venue
- Frontiers in Cellular Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2014-04-03
- Volume
- 8
- Pages
- 97-97
- ISSN
- 1662-5102 (ISSN-L)
- PMC
- PMC3982075
- OpenAlex
- W2029961705
- Cited by
- 186
- References
- 346
- Citations by year
- 2026: 10 · 2025: 16 · 2024: 20 · 2023: 18 · 2022: 16 · 2021: 19 · 2020: 29 · 2019: 12 · 2018: 12 · 2017: 10 · 2016: 12 · 2015: 9 · 2014: 2
- FWCI
- 0.89
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- Funders
- Medical Research Council
- National Health and Medical Research Council (1043771)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- environmental enrichment, neuroimmunomodulation, physical activity, cytokines, interleukin-6, Toll-like receptors, adipokines, microglia, T cells, natural killer cells, social defeat, sensory enrichment, IL-1β, TNF-α, IL-10, mental illness
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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