Uncovering the role of microglia in fetal alcohol spectrum disorders

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Representative images of Iba-1+ microglia in the postnatal day 10 rat hippocampus. Image courtesy of Anna Klintsova, PhD.

Children born with fetal alcohol spectrum disorders face a range of physical and cognitive impairments including long-term deficits in learning, behavior, and immune function. In a paper published in Neuroscience, Dr. Anna Klintsova and her lab at the University of Delaware report that activation of the brain’s immune response may contribute to some of the damage caused by fetal alcohol spectrum disorders.

In their study, the researchers used Stereo Investigator and Neurolucida to examine the hypothesis that exposure to alcohol while the brain is growing rapidly is associated with abnormal microglial activation and high levels of pro-inflammatory proteins which impair learning-related plasticity; leading to neuro-developmental and psychopathological disorders.

“My lab has been using both Stereo Investigator and Neurolucida for more than a decade in all quantitative neuroanatomical studies, including the featured one,” said Dr. Anna Klintsova. “We find this software to be user-friendly, reliable and essential for obtaining unbiased results.”

They used Stereo Investigator to quantify the number of microglia in the hippocampus of neonatal rats who were exposed to alcohol during the equivalent of the third trimester of a human pregnancy. The researchers expected to see an increased number of microglia in alcohol-exposed neonatal rats, however they found a decreased number of microglia. Despite the decrease in microglia number, there was a significant increase in pro-inflammatory proteins expressed by microglia and an increase in microglial activation.

To measure microglial activation, the researchers quantified the area of cell territory using Neurolucida. Activated microglia have a smaller cell territory than resting microglia, so the smaller cell territory found in alcohol exposed rats indicates a more active state.

This research supports the hypothesis that abnormal microglia activation plays a role in fetal alcohol spectrum disorders, however more research is needed to further understand the relationship.

Boschen, K., Ruggiero, M.J., Klintsova, A.Y., (2016) Neonatal binge alcohol exposure increases microglial activation in the developing rat hippocampus. Neuroscience 324: 355–366. DOI: 10.1016/j.neuroscience.2016.03.033

 

Iron Deficiency Worsens Fetal Alcohol Spectrum Disorders

An immunostained image of myelin basic protein in the cerebella of a mouse brain with an iron-sufficient diet compared with the brain of a mouse exposed to alcohol and fed an iron-insufficient diet. It shows the reduced cerebellar size due to the ID-alcohol combination. Green is MBP immunostain, blue is DAPI for nuclei.

An immunostained image of myelin basic protein in the cerebella of a mouse brain with an iron-sufficient diet compared with the brain of a mouse exposed to alcohol and fed an iron-insufficient diet. It shows the reduced cerebellar size due to the ID-alcohol combination. Green is MBP immunostain, blue is DAPI for nuclei. Image courtesy of Susan Smith, PhD.

If a pregnant woman drinks alcohol, she risks giving birth to a baby with physical and cognitive deficits – characteristics of fetal alcohol spectrum disorders. In a new study, researchers say that when the mother is low in iron, the consequences are even worse.

The scientists examined two groups of pregnant rats – one group was fed an iron sufficient diet while the other was fed a diet with insufficient iron levels. The offspring from both groups were exposed to alcohol from 4 to 9 days after birth – a time when their brains are going through a growth spurt and are particularly sensitive to alcohol. They were compared to offspring who received an iron-sufficient diet but were not exposed to alcohol. This growth spurt correlates to a growth spurt in humans that occurs during the third trimester of pregnancy.

The researchers used delay and trace eye blink classical conditioning methods to assess the offspring’s learning and memory. Learning impairments were reported in both alcohol-exposed groups regardless of their iron status, but more extreme impairments were seen in iron deficient rats compared to iron sufficient rats. After the behavioral tests were completed, the researchers studied the cerebellum and hippocampus – brain regions involved in learning and memory – at a cellular level.

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