Time Course of Blood and Brain Cytokine/Chemokine Levels Following Adolescent Alcohol Exposure and Withdrawal in Rats

Abstract

Background: Adolescence is a critical period for neural development, and alcohol exposure during adolescence can lead to an elevated risk for health consequences as well as alcohol use disorders. Clinical and experimental data suggest that chronic alcohol exposure may produce immunomodulatory effects that can lead to the activation of pro-inflammatory cytokine pathways as well as microglial markers. The present study evaluated, in brain and blood, the effects of adolescent alcohol exposure and withdrawal on microglia and on the most representative pro-and anti-inflammatory cytokines and major chemokines that can contribute to the establishing of a neuroinflammatory environment.Methods: Wistar rats (males, n = 96) were exposed to ethanol (EtOH) vapors, or air control, for 5 weeks over adolescence (PD22-PD58). Brains and blood samples were collected at 3 time points: (i) after 35 days of vapor/air exposure (PD58); (ii) after 1 day of withdrawal (PD59), and (iii) 28 days after withdrawal (PD86). The ionized calcium-binding adapter molecule 1 (Iba-1) was used to index microglial activation, and cytokine/chemokine responses were analyzed using magnetic bead panels.Results: After 35 days of adolescent vapor exposure, a significant increase in Iba-1 immunoreactivity was seen in amygdala, frontal cortex, hippocampus, and substantia nigra. However, Iba-1 density returned to control levels at both 1 day and 28 days of withdrawal except in the hippocampus where Iba-1 density was significantly lower than controls. In serum, adolescent EtOH exposure induced a reduction in IL-13 and an increase in fractalkine at day 35. After 1 day of withdrawal, IL-18 was reduced, and IP-10 was elevated, whereas both IP-10 and IL-10 were elevated at 28 days following withdrawal. In the frontal cortex, adolescent EtOH exposure induced an increase in IL-1b at day 35, and 28 days of withdrawal, and IL-10 was increased after 28 days of withdrawal.Conclusion: These data demonstrate that EtOH exposure during adolescence produces significant microglial activation; however, inflammatory markers seen in the blood appear to differ from those observed in the brain.

Characterization of Early-Stage Alcoholic Liver Disease with Hyperhomocysteinemia and Gut Dysfunction and Associated Immune Response in Alcohol Use Disorder Patients

“…As with analysis of alcohol withdrawal, we added markers of the gut-liver axis and proinflammatory response to the analysis and found a significant increase in the effect on ALT. Studies on both animal and human models support that chronic alcohol exposure induces gut-derived altered immunomodulatory effects, leading to the activation of proinflammatory cytokine pathways, [ 45 , 46 ] as was also observed in our study. Thus, there was a multifactorial consequence in the liver injury.…”

The impact of early life stress and immune challenge on behavior and glia cells alteration in late adolescent rats

“…The effects of early life stress as well as other environmental stressors have been investigated in the context of microglial activation during development. Indeed, alcohol exposure in the intrauterine life or adolescence period, maternal immune activation, mother's sleep deprivation or valproic acid contact, as well as gut microbiota impairment lead to microglial activation and morphological changes in the offspring (Antonson et al., 2019; Carlessi et al., 2021; Lucchina & Depino, 2014; Sanchez‐Alavez et al., 2019; Zhang et al., ,,2016, 2018). Microglia cells seem to be involved in the neurotrophic factors release and synaptogenesis, which can be affected by abnormal microglial activation and then, be involved with psychiatric conditions (Réus, Fries, et al., 2015; Réus et al., 2018).…”

Pairing Binge Drinking and a High-Fat Diet in Adolescence Modulates the Inflammatory Effects of Subsequent Alcohol Consumption in Mice

“…Most importantly, blocking the alcohol-induced neuroimmune response by genetic elimination of TLR4 has prevented some long-term behavioral impairments [ 35 ]. Furthermore, the involvement of the immune response in modulating the neuropathological consequences induced by adolescent BD has also been described [ 36 , 37 , 38 ].…”