Severe infections during pregnancy can cause impaired development in the brain of the fetus, research with mice shows.
The mother’s health is important for the fetus’s brain development during pregnancy. Many factors play key roles for healthy brain development, including nutrition, stress, hormonal balance, and the mother’s immune system.
Researchers have observed in both humans and animals that severe infections in the pregnant mother are a risk factor for developing psychiatric disorders such as schizophrenia and autism spectrum disorders later in life for the offspring.
The new research shows how these infections can cause impaired development of stem cells and precursor cells to neuronal cells in the fetal brain.
“The connection has been made in animal studies and clinical observation studies. However, this is the first time that we show how infections during pregnancy affect brain development and can lead to cognitive impairment,” says Konstantin Khodosevich, associate professor in the Biotech Research and Innovation Centre (BRIC) at the University of Copenhagen.
“While many factors have been hypothesized or indicated, it is important that we show the steps of neuronal development that are actually affected.”
Infections during pregnancy and psychiatric disorders
The researchers studied the development of neurons in mice. The mother’s immune response to infection had an effect stretching from stem cells and precursor cells to neuronal cells leading to profound disruption in their development in the brain.
More specifically, the development of cortical GABAergic interneurons—the key neuronal class that provides inhibition in the brain—was impaired. The effect was immediate and cascaded to dramatic long-lasting impairments, thus resulting in multiple “hits” during the process of neuronal development—from the time neurons are born to the time they mature.
Furthermore, the researchers also concluded that the newborn mice showed symptoms resembling those from human psychiatric disorders including decreased prepulse inhibition, altered social interactions, and cognitive decline.
“There are big technological and ethical issues about studying this in humans because of the vulnerability of pregnant women. That is why we study how the mechanisms work in mice. Psychiatric disorders are really complex and for some of them, we are still only guessing how they arise. We really want to contribute to the scientific understanding of these diseases,” says Khodosevich.
Timing is key
Showing the effects of having the infections at different times during the pregnancy was one of the major findings of the study. Infections at different times affected different precursor cells, and as a result different neurons. This means that the timing of infection is very important and can lead to varying outcomes based on which stage of brain development is affected. This could potentially underlie the complexity of psychiatric disorders.
The researchers are now looking forward to diving deeper into the molecular mechanisms and signaling pathways behind the impairment of the interneuron development.
The new study appears in the journal Molecular Psychiatry.
Funding for the study came from the Hallas Møller Grant from the Novo Nordisk Foundation, the Lundbeck Foundation, NIH Brain Initiative, and the Independent Research Fund Denmark.
Source: University of Copenhagen
