Impact of Alcohol on Neuroinflammation

Addiction is common within the U.S. Alcohol use disorder is one type of substance abuse. Dependency on alcohol may begin as early as adolescence, which is a crucial time for development. During adolescence, the brain undergoes maturational processes that are necessary for a cognitive function later in life. Rodent studies have shown that the medial prefrontal cortex (mPFC) and the hippocampus, are susceptible to damage from alcohol. We have previously found a greater loss of myelin of axons in the mPFC in adolescent males (Tavares et al., 2019). In this study, we test the hypothesis that voluntary alcohol drinking during adolescence leads to a greater inflammatory response in males compared to females. Adolescent male and female Wistar rats self-administered sweetened alcohol or sweetened water. Brains were collected and immunolabeled for ionized calcium-binding adapter molecule 1 (Iba-1). Microglial cell morphology was then analyzed using high-content microscopy. There was no effect of sex on cumulative alcohol intake. Microglia density in the mPFC did not change for males or females. In the mPFC, there was a decrease in branching points per microglia cell distribution in both males and females. For the hippocampus, there were differences found in microglia density in males, and the microglia population shifted to a state of having fewer ramifications per cell in the alcohol group in the CA1 and DG of females, and in the CA2/3 of both males and females. No differences were found in the circularity of microglia in the hippocampus. The lack of consistent findings regarding a greater extent of microglia activation in males do not support our hypothesis that differential microglia activation is responsible for the sex differences in the myelination of axons.