The changes in behavior that come about under the influence of alcohol, such as difficulty controlling muscles for walking and talking, may be influenced by immune cells in the brain, according to a new study from Australia published in the British Journal of Pharmacology this month.
Lead author Dr Mark Hutchinson, Australia Research Council (ARC) Research Fellow with the School of Medical Sciences at the University of Adelaide, told the press he and his colleagues had uncovered new evidence that immune responses in the brain were involved in behavioral responses to alcohol.
“Alcohol is consumed annually by two billion people world-wide with its abuse posing a significant health and social problem,” said Hutchinson, “Over 76 million people are diagnosed with an alcohol abuse disorder.”
“It’s amazing to think that despite 10,000 years of using alcohol, and several decades of investigation into the way that alcohol affects the nerve cells in our brain, we are still trying to figure out exactly how it works,” he noted.
For their study, Hutchinson and colleagues gave laboratory mice a single shot of alcohol and examined what happened to the animals’ behavior when they blocked their toll-like receptors. Specifically they blocked toll-like receptor 4 (TLR4) because, as they write in their introduction:
” Emerging evidence implicates a role for toll-like receptor 4 (TLR4) in the central nervous system effects of alcohol. “
Toll-like receptors activate the immune system when they encounter foreign substances, such as molecules derived from microorganisms (remember alcohol is made by yeast), breaching certain barriers to and inside the body, such as the skin and the gut wall.
The researchers were interested in finding out if blocking a particular pathway that was responsible for “TLR4-MyD88- dependent signalling” would interfere with the acute behavioural actions of alcohol. They also wanted to find out if alcohol could trigger certain pathways downstream of TLR4.
They used two ways to block the receptors: chemically, using drugs to inhibit TLR4 signalling, and genetically, by engineering mice with inactivated genes that code for the receptor.
They found that both methods significantly reduced the effect of alcohol and decreased the recovery time compared to controls. (To establish this they measured both sedation and motor impairment, the latter using tests called “loss of righting reflex, LORR, and rotarod).
Hutchinson said these findings show that blocking this part of the immune system, either genetically or with drugs, reduced the behavioral effects of alcohol.
He said he believes they would find similar results with humans and that they would add to our understanding of how alcohol affects us, “as it is both an immunological and neuronal response”.
“Such a shift in mindset has significant implications for identifying individuals who may have bad outcomes after consuming alcohol, and it could lead to a way of detecting people who are at greater risk of developing brain damage after long-term drinking,” he said, explaining that drugs targeting TLR4 could help treat alcohol addiction and overdoses.
Written by Catharine Paddock