Lifelong Impacts of Moderate Prenatal Alcohol Exposure on Neuroimmune Function

Abstract

In utero alcohol exposure is emerging as a major risk factor for lifelong aberrant neuroimmune function. Fetal alcohol spectrum disorder encompasses a range of behavioral and physiological sequelae that may occur throughout life and includes cognitive developmental disabilities as well as disease susceptibility related to aberrant immune and neuroimmune actions. Emerging data from clinical studies and findings from animal models support that very low to moderate levels of fetal alcohol exposure may reprogram the developing central nervous system leading to altered neuroimmune and neuroglial signaling during adulthood. In this review, we will focus on the consequences of low to moderate prenatal alcohol exposure (PAE) on neuroimmune interactions during early life and at different stages of adulthood. Data discussed here will include recent studies suggesting that while abnormal immune function is generally minimal under basal conditions, following pathogenic stimuli or trauma, significant alterations in the neuroimmune axis occur. Evidence from published reports will be discussed with a focus on observations that PAE may bias later-life peripheral immune responses toward a proinflammatory phenotype. The propensity for proinflammatory responses to challenges in adulthood may ultimately shape neuron–glial-immune processes suspected to underlie various neuropathological outcomes including chronic pain and cognitive impairment.

Relationship of Wine Consumption with Alzheimer’s Disease

“…Taken together, the results of numerous studies indicate that neuroimmune signaling plays a key role in the development of alcohol-related brain disorders. Chronic ethanol sensitizes both systemic and brain responses to the neuroimmune-gene, resulting in the hypothalamic-pituitary-adrenal (HPA)-mediated enhancement of peripheral cytokines, which further exacerbates the neuroimmune response, which increases neurodegeneration [87][88][89][90]. In addition to neuroimmune signaling, glutamate excitotoxicity also is linked to alcoholic neurodegeneration.…”

Adverse health outcomes associated with fetal alcohol exposure: A systematic review focused on immune‐related outcomes

“…However, it is also important to consider that although infection outcomes were not documented, previous research has suggested that low levels of PAE may underlie susceptibility to the development of autoimmune diseases through dysregulated cytokine production . Notably, preclinical research has demonstrated that both peripheral and central cytokines as well as C‐reactive protein (CRP), a marker of inflammation, were altered in female rat offspring with PAE.…”

“…18 These studies were conducted in children of different ethnicities, and consequently, this is an area that requires further research in However, it is also important to consider that although infection outcomes were not documented, previous research has suggested that low levels of PAE may underlie susceptibility to the development of autoimmune diseases through dysregulated cytokine production. 44 Notably, preclinical research has demonstrated that both peripheral and central cytokines 8 as well as C-reactive protein (CRP), 39 a marker of inflammation, were altered in female rat offspring with PAE. Specifically, animals showed increased pro-inflammatory cytokines in serum, hippocampus, and prefrontal cortex and decreased levels in the spleen and hypothalamus 8 and increased serum CRP.…”

Relationship between Wine Consumption and Alzheimer's Disease

“…Taken together, the results of numerous studies indicate that neuroimmune signaling play a key role in the development of alcohol-related brain disorders. Chronic ethanol sensitizes both systemic and brain responses to neuroimmune-gene resulting in the hypothalamic-pituitaryadrenal-(HPA)-mediated enhancement of peripheral cytokines, which further exacerbates the neuroimmune response which increases neurodegeneration [67][68][69][70]. In addition to neuroimmune signaling, glutamate excitotoxicity also is linked to alcoholic neurodegeneration.…”