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.
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.
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-1β at day 35, and 28 days of withdrawal, and IL-10 was increased after 28 days of withdrawal.