Cellular and molecular mechanisms of immunomodulation in the brain through environmental enrichment

Abstract

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.

Does environmental enrichment promote recovery from stress in rainbow trout?

“…There is a plethora of evidence supporting the benefits of enrichment for animals held in captivity, particularly mammals (Simpson and Kelly, 2011;Singhal et al, 2014). However, evidence for the benefits or otherwise of enriched environments for fish is lacking.…”

“…In laboratory rodent studies, enrichment can improve the health and welfare of the test subjects but may also reduce individual variation such that the data sets are more robust and scientifically valid (Singhal et al, 2014). The present study was conducted to investigate the effects of simple environmental enrichment on (i) the recovery of rainbow trout from stressors and invasive procedures, and (ii) the degree of interindividual variability among the data collected.…”

Environmental Enrichment Improves Behavior, Cognition, and Brain Functional Markers in Young Senescence-Accelerated Prone Mice (SAMP8)

“…EE causes a significant change in the genetic expression of genes that are involved in neuronal structure, plasticity, and neurotransmission [12]. Furthermore, EE can affect cytokine production and glial cell function [13]. Taken together, evidence indicates that EE can modulate brain function by improving learning and memory and reducing memory loss in rodents.…”

Pointing the finger at proton pump inhibitors

“…listening to music), have shown that EE improves cognition and memory. [20] Although more work is required, this study suggests that similar non-pharmacological approaches may be relevant to treat depression associated with stress and diabetes.…”