College of Medicine

Michelle Arbeitman usually studies the reproductive behaviors of fruit flies, analyzing which genes get turned on or off in neurons that direct behaviors. But when she looked for the same information in mice, another widely used laboratory animal model, she came up short. To fill in the gaps, the biomedical sciences researcher teamed up with Richard Nowakowski, department chair, to find the missing information on the gene expression changes in the mouse maternal brain.

The knowledge they gained was recently published in G3: Genes|Genomes|Genetics, and in follow-up studies it may contribute to understanding mental health disorders and other pregnancy complications in humans.

“People have examined different brain regions, but nothing has been as comprehensive as our study,” said Arbeitman. “We looked in the hypothalamus, the hippocampus, the neocortex and the cerebellum at six different stages.”

The hypothalamus was chosen because it is involved in many hormonal changes that trigger progression through pregnancy, birth and postpartum periods. The neocortex and hippocampus were chosen given their known roles in higher-order brain functions, including learning and cognition. They have also been implicated in responding to hormonal changes but have not been thoroughly examined. The cerebellum, a region of the brain responsible for motor control, was selected to serve as the “control tissue” to measure base change.

Arbeitman and Nowakowski looked at gene expression (genes turning on and off) in each of the brain regions during two pregnancy time points and three postpartum time points. Then they compared their findings with a virgin control group.

“The number of genes that changed in the pregnant and new mothers gives the appearance of a major developmental transformation,” said Arbeitman.

Nowakowski agreed.

“Previously there were no good data available on what is happening in the brain of the mother,” he said. “The approach that we used, next-generation sequencing, allows us to monitor the changes in the expression of thousands of genes simultaneously in several regions of the brain. The results show that the experience of pregnancy changes the brain during the days before and after giving birth.”

Arbeitman hopes to conduct future research on how permanent the maternal brain changes are and hopes to identify the critical neurons for maternal behaviors. Of interest is whether maternal behaviors are more influenced by genes inherited from the mother or father. The comprehensive nature of the current study, however, helps fill the genomic gap in the literature.

“It gives us more insight into how robust the changes are in the brain,” said Arbeitman. “It suggests that many regions of the brain are involved in the maternal transition. It will be interesting to determine if there are dedicated circuits of neurons for reproductive behaviors in mice, like we observe in fruit flies, or if the potential for maternal behaviors is more broadly distributed in many neurons throughout the brain.”

And there are human health implications.

“This could provide a roadmap on the biology of the maternal brain,” said Arbeitman. “It’s a more rational approach to therapeutic interventions. Understanding the basic biology could help prevent pregnancy complications caused by hormonal release, like pre-term birth, and will contribute to understanding postpartum mental health disorders, especially their molecular basis.”