Research continues to rule out brain’s immune system as key to fetal alcohol spectrum disorders

May. 8, 2023


A new study out in Frontiers in Neuroscience found early alcohol exposure does not change the connection between the brain's immune system and neurons that send information related to functions like balance and memory.

Researchers in the Majewska Lab at the Del Monte Institute for Neuroscience at the University of Rochester investigated the interaction between microglia and Purkinje neurons—the neurons responsible for sending information from the cerebellum. They found mice exposed to ethanol during development had no differences in microglia movement or structure and only subtle changes in the interaction between microglia and Purkinje neurons. “It appears that developmental ethanol exposure has little effect on microglia later in life,” said MaKenna Cealie, a Neuroscience graduate student in the lab and first author of the paper. “We believe examining other cell types and their interactions may be an important direction for future fetal alcohol spectrum disorders (FASD) studies to take.”

Other authors include the senior author Ania Majewska, PhD, Linh Le, Erik Vonkaenel, and Matthew McCall, PhD, of the University of Rochester Medical Center, and James Douglas and Paul Drew, PhD, of the University of Arkansas Medical Center.

The research was supported by the National Institutes of Health (NIH), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), and the University of Rochester Intellectual and Developmental Disabilities Research Center (UR-IDDRC).

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Original article posted on Nov. 2, 2021

Woman sitting with glass of wine on a table in front of her

Researchers at the Del Monte Institute for Neuroscience at the University of Rochester continue to find evidence that the brain’s immune system may not be the culprit behind fetal alcohol spectrum disorders (FASD). It has long been thought that cells in the brain’s immune system called microglia are responsible for the neurological damage that occurs when this type of exposure happens.

“We looked for more subtle changes in microglia function this time,” said Ania Majewska, PhD, professor of neuroscience at the Del Monte Institute for Neuroscience, and lead author on the study published in Developmental Neurobiology. “We were not able to detect a difference in function leading us to believe that the defect may exist in other cell types. However, given the heterogeneity and complexity of microglial function, we are also exploring how different populations of microglia in different parts of the brain respond to alcohol.”

One out of every 100 babies born in the U.S. is diagnosed with FASD, which occurs when a child is exposed to alcohol in the womb. FASD can cause lifelong physical and cognitive impairments, such as poor impulse control and attention, learning disabilities, compromised fine motor skills, and delays in the ability of the brain to process visual and auditory information. There is no available treatment for FASD.

Majewska’s research initially poked holes in the idea that FASD is driven by damage caused in the brain by impaired microglia when her lab found no difference in microglia activity in the brains of mice exposed to alcohol early in development when compared to those who were not exposed.

In this recent work, researchers exposed mice to alcohol early in development and looked beyond the baseline of microglial movement. Using advanced imaging technology called two-photon microscopy the scientists observed how the microglia interacted with neuronal dendrites – part of the connection between neurons that enables neighboring nerves cells to communicate. They found no difference in this connection when comparing brains exposed to alcohol to brains that were not.

“The brain is made up of many neuronal types so it is possible other microglia-neuron interactions are changing, but it is not a general phenomenon,” said Majewska. “But just because these are immune cells doesn’t mean that they will be involved in every disorder or developmental perturbation. Narrowing down their exact roles is important in terms of targeting these cells for therapies for neurodevelopmental disorders.”

Additional co-authors of the study include Elissa Wong, Alexandra Strohm, Jason Atlas, and Cassandra Lamantia with the University of Rochester Medical Center. The research was funded by National Institute on Alcohol Abuse and Alcoholism.