Early-Life Programming of Later-Life Brain and Behavior: A Critical Role for the Immune System

By S. Bilbo, J. Schwarz. Frontiers in Behavioral Neuroscience, 2009

637 citations recorded by the source corpus.

The immune system is well characterized for its critical role in host defense. Far beyond this limited role however, there is mounting evidence for the vital role the immune system plays within the brain, in both normal, “homeostatic” processes (e.g., sleep, metabolism, memory), as well as in pathology, when the dysregulation of immune molecules may occur. This recognition is especially critical in the area of brain development. Microglia and astrocytes, the primary immunocompetent cells of the CNS, are involved in every major aspect of brain development and function, including synaptogenesis, apoptosis, and angiogenesis. Cytokines such as tumor necrosis factor (TNF)α, interleukin [IL]-1β, and IL-6 are produced by glia within the CNS, and are implicated in synaptic formation and scaling, long-term potentiation, and neurogenesis. Importantly, cytokines are involved in both injury and repair, and the conditions underlying these distinct outcomes are under intense investigation and debate. Evidence from both animal and human studies implicates the immune system in a number of disorders with known or suspected developmental origins, including schizophrenia, anxiety/depression, and cognitive dysfunction. We review the evidence that infection during the perinatal period of life acts as a vulnerability factor for later-life alterations in cytokine production, and marked changes in cognitive and affective behaviors throughout the remainder of the lifespan. We also discuss the hypothesis that long-term changes in brain glial cell function underlie this vulnerability.

Subfields: Behavioral Neuroscience, Biological Psychiatry, Neurology

View Paper: https://www.semanticscholar.org/paper/0f67d85760c60cf472eb2d9c637a1ff58cd709d2

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Behavioral Neuroscience

1. Gregory E. Miller
2. A. Danese
3. E. Chen
4. Bruce S. McEwen
5. K. J. Parker
6. V. Perry
7. R. Reshef
8. R. Yirmiya

In Biological Psychiatry

1. A. Danese
2. E. Chen
3. Gregory E. Miller
4. V. Perry
5. Bruce S. McEwen
6. R. Reshef
7. R. Yirmiya
8. Rajita Sinha

In Neurology

1. V. Perry
2. Gregory E. Miller
3. Bruce S. McEwen
4. A. Danese
5. Amanda Sierra
6. R. Yirmiya
7. C. Cunningham
8. R. Ransohoff

Citations in the corpus

• Psychological Stress in Childhood and Susceptibility to the Chronic Diseases of Aging: Moving Towards a Model of Behavioral and Biological Mechanisms (2011, background): “These findings have fueled interest in whether the psychosocial environment might also have a role in calibrating the immune system’s response tendencies (Bilbo & Schwarz, 2009; Coe & Lubach, 2005, 2007; Finch & Crimmins, 2004; McDade, 2005; Prescott, 2006; Wright, 2007).”
• Depression as a microglial disease. (2015, background): “Early stress alters immune functioning at the time of exposure, but it can also change immune, endocrine, neural, and behavioral responsiveness to various stressful challenges later in life and contribute to various psychopathologies [66,67].”
• Coupled Proliferation and Apoptosis Maintain the Rapid Turnover of Microglia in the Adult Brain (2017, background): “…shown genes (thicker lines indicate more shared genes). al (blue), CD45low (green), or CD45high (yellow) Vav- eports 18, 391–405, January 10, 2017 401 (Bilbo and Schwarz, 2009), delayed inflammation after traumatic brain injury (TBI) (Johnson et al., 2013), or the onset of agerelated amyloid…”
• Adverse childhood experiences, allostasis, allostatic load, and age-related disease. (2012, background): “For example, experimental work in animal models showed that childhood infection influences adult behavior, HPA axis activity, and immune system functioning [158,159].”