Impact of Prenatal and Subsequent Adult Alcohol Exposure on Pro-Inflammatory Cytokine Expression in Brain Regions Necessary for Simple Recognition Memory

Abstract

Microglia, the immune cells of the brain, are important and necessary for appropriate neural development; however, activation of microglia, concomitant with increased levels of secreted immune molecules during brain development, can leave the brain susceptible to certain long-term changes in immune function associated with neurological and developmental disorders. One mechanism by which microglia can be activated is via alcohol exposure. We sought to investigate if low levels of prenatal alcohol exposure can alter the neuroimmune response to a subsequent acute dose of alcohol in adulthood. We also used the novel object location and recognition memory tasks to determine whether there are cognitive deficits associated with low prenatal alcohol exposure and subsequent adulthood alcohol exposure. We found that adult rats exposed to an acute binge-like level of alcohol, regardless of gestational alcohol exposure, have a robust increase in the expression of Interleukin (IL)-6 within the brain, and a significant decrease in the expression of IL-1β and CD11b. Rats exposed to alcohol during gestation, adulthood, or at both time points exhibited impaired cognitive performance in the cognitive tasks. These results indicate that both low-level prenatal alcohol exposure and even acute alcohol exposure in adulthood can significantly impact neuroimmune and associated cognitive function.

Environmental Enrichment During Adolescence Mitigates Cognitive Deficits and Alcohol Vulnerability due to Continuous and Intermittent Perinatal Alcohol Exposure in Adult Rats

“…Taken together, our data are in line with previous reports demonstrating that chronic prenatal exposure to low-tomoderate doses of alcohol is sufficient to induce decreased behavioral reactivity in the open field (Kleiber et al, 2011) and declarative memory deficits in the novel object recognition test (Dandekar et al, 2019), together with a detrimental impact on the neuroimmune function of the perirhinal cortex (Terasaki and Schwarz, 2017). On the other hand, repeated low-dose prenatal alcohol exposure does not produce detrimental effects on pyramidal cells within the dorsal hippocampus or does not impair spatial learning and memory performance in the MWM (Cullen et al, 2014).…”

Lifelong Impacts of Moderate Prenatal Alcohol Exposure on Neuroimmune Function

“…In addition to the PAE sex-specific differences in chemokines/cytokines, the same report demonstrated increased levels of CD11b and brain-derived neurotropic factor in adult brain examined on PND 90 ( 51 ). These data indicate that long-term immune activation in different brain regions does not require a parallel induction of cytokines.…”

“…In a more recent study, PAE rats were further exposed to an acute binge-like dose of alcohol in adulthood ( 51 ). This study revealed that PAE exaggerated IL-6 production in the prefrontal cortex following alcohol exposure in adulthood, suggesting that adult alcohol exposure may act as a neuroinflammatory agent.…”

“…Females (with PAE alone) and males with PAE in combination with an acute binge-dose of alcohol were deficient in learning the NOL task. In addition, male PAE animals and PAE plus an acute binge-like dose of alcohol in adulthood (in both males and females) negatively impacted performance the NOR task ( 51 ). Together, these data highlight that low/moderate levels of PAE can negatively impact cognitive function in later life, and these long-term consequences can be exacerbated by subsequent challenges (e.g., binge-like doses of alcohol exposure or immune activation).…”

Lingering Effects of Prenatal Alcohol Exposure on Basal and Ethanol-Evoked Expression of Inflammatory-Related Genes in the CNS of Adolescent and Adult Rats

“…One possibility for this outcome is that the single acute ethanol challenge administered here was not optimal for revealing such prenatal-postnatal interactions based on the dose utilized (i.e., we may be observing a ceiling effect after a 4 g/kg administration) or time point examined (i.e., PAE may alter the kinetics of the immune response to acute challenge and we did not select an optimal time to capture PAE vs. FCL effects in response to the challenge). To fully reveal lingering PAE effects, repeated exposures to ethanol might be required to observe more significant consequences of PAE (e.g., similar to the two consecutive ethanol binges in Terasaki and Schwarz, 2017), or there may be other time points (e.g., withdrawal; Topper et al, 2015) at which PAE effects would be more evident. Furthermore, it is possible that other brain regions, such as the prefrontal cortex (Terasaki and Schwarz, 2017), might be more sensitive to lasting effects of PAE on cytokines and chemokines, and their responsiveness to acute ethanol.…”