Immune Activity During Pregnancy Tied to Neuronal Defects, Anxiety, and Cognitive Impairments

Apple blossoms

I’m definitely cataloguing this in the Interesting category!

Neurons called Parvalbumin Interneurons in the brains of mice pups were underactive when their mothers had an infection while pregnant, i.e. the mother’s immune systems were ramped up due to the infection. This did not happen to mice whose mothers had no infection during pregnancy. The mice with underactive Parvalbumin Interneurons exhibited more anxiety and struggled with behavioral tests.

Also it was possible to induce these effects (anxiety and difficulty in behavioral tests) in normal mice (no infection in mother while pregnant) by shutting off the Parvalbumin Interneurons.

Parvalbumin Interneurons are neurons which send inhibitory signals to other neurons are much weaker in neurons of mice born to mothers whose immune system had been activated during pregnancy. “Parvalbumin interneurons help coordinate the activity of other cells in the brain, and are thought to be important for memory and cognitive flexibility. Reduced numbers and structural abnormalities in parvalbumin interneurons have been linked to multiple psychiatric disorders…”

https://bbrfoundation.org/brain-matters-discoveries/immune-activity-during-pregnancy-tied-to-neuronal-defects-anxiety-and

Researchers are investigating the possibility that infections during pregnancy increase the likelihood that the fetus will develop into a person who will have mental illness later in life. There is evidence that immune activity in response to maternal infections may increase the offspring’s risk of schizophrenia,bipolar disorder, depression, and anxiety disorders.

In a new animal study led by Christoph Kellendonk, Ph.D., a 2002 and 2008 NARSAD Young Investigator at Columbia University Medical Center, scientists have shown that inhibitory brain cells called parvalbumin interneurons are particularly vulnerable to such maternal immune activation. These cells do not signal as they should in mice whose mothers’ immune systems are activated during pregnancy, the researchers have shown. What’s more, the signaling problems are associated with cognitive impairments and anxiety-like behavior in mice.

Activated immune system in pregnant mice linked to later cognitive impairments in their offspring. Tweet >

The research team, which included Alan Stewart Brown, M.D., M.P.H., a 1993, 1996 Young Investigator, 2000, 2004 Independent Investigator and 2015 Distinguished Investigator, 2013 Young Investigator Sarah E. Canetta, Ph.D. and BBRF Scientific Council Member and 2001, 2003 Young Investigator Joshua A. Gordon, M.D., Ph.D., all at Columbia, published its findings February 2 in the journal Molecular Psychiatry.

Parvalbumin interneurons help coordinate the activity of other cells in the brain, and are thought to be important for memory and cognitive flexibility. Reduced numbers and structural abnormalities in parvalbumin interneurons have been linked to multiple psychiatric disorders, but so far it has been difficult to assess how these abnormalities affect brain function.

In their mouse study, Dr. Kellendonk and colleagues determined that the inhibitory signals that parvalbumin interneurons usually send to target cells are much weaker than usual in mice whose mothers’ immune systems had been active during pregnancy. Those mice struggled with a behavioral test that involved task switching, suggesting certain cognitive impairments, and also exhibited more anxiety than mice whose mothers had no immune activation during pregnancy.

In mice whose mothers did not have activated immune systems during pregnancy, the scientists could provoke the same increase in anxiety and cognitive defects simply by artificially shutting off parvalbumin interneurons, supporting the idea that defects in the cells were responsible for the affected animals’ behavior.

Takeaway: Study in mice identifies brain cells that are vulnerable to a mother’s infection during pregnancy. Reduced signaling from these cells was associated with increased anxiety and cognitive impairments.

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