Molecular Signatures of a Broken Heart

The transcriptional profiles in the brains of prairie voles changed after a long breakup, revealing a molecular shift that might help them cope with the loss of a partner.

Black and white portrait by Mariella Bodemeier Loayza Careaga, PhD
| 4 min read
The image shows two adult prairie voles. The voles have a brown coat and are touching each other’s snouts.

Scientists use the socially monogamous prairie voles (Microtus ochrogaster) to investigate the molecular basis of bond formation and disruption.

Paul Muhlrad

Register for free to listen to this article
Listen with Speechify
0:00
4:00
Share

Losing a partner is a distressing experience for humans. Apparently, that is also the case for prairie voles. These furry little rodents can form lifelong bonds and share parenting and household responsibilities such as defending their underground burrows. Like most people, prairie voles also adapt to the loss of a partner over time,1 suggesting that they might be good models for understanding loss adaptation in the brain.

In a study published in eLife, a research team led by Zoe Donaldson, a neuroscientist at the University of Colorado Boulder, examined prairie vole brains to get insights into the transcriptional changes after bond formation and disruption. They found that pair bonding stimulated the expression of hundreds of genes, and separating the furry couples for weeks, but not days, downregulated this transcriptional signature.2

“There has been some work on partner loss in voles,” said Larry Young, a neuroscientist at Emory University who was not involved in the research. “This is the first time researchers looked at changes in gene expression.”

See “Monogamous Rodents Don’t Need “Love Molecules” To Pair Up

To investigate the effects of partner loss in the brain, Donaldson and her team housed vole couples together for two weeks and then separated some of the mating couples for either two days or four weeks. They selected those time points since their previous work suggested that voles can form a new bond after a four-week breakup.1

The team first looked at the behavioral effects of partner separation through an experiment in which a vole must choose between spending time with its partner or a stranger. Neither the brief nor long separation altered the voles’ preferences for their partners, suggesting that this core feature of the relationship remains intact despite the physical separation.

It would be wonderful if, as a society, we got better at sort of learning what loss looks like, what grieving looks like, and how to help those people who are grieving.

—Zoe Donaldson, University of Colorado Boulder

The researchers next investigated gene expression changes after partner separation using RNA sequencing. They focused on the nucleus accumbens, a brain region implicated in romantic relationships and grieving in humans. Pair-bonded voles showed stable upregulation of several genes involved in many different brain processes, such as the formation of synapses and signaling pathways relevant for learning. The team found that this upregulation trend was reversed in animals separated for four weeks.

Many of the pair bonding upregulated genes were associated with glial cell functioning. “We didn’t anticipate the role of glia in this process,” said Julie Sadino, a postdoctoral researcher in Donaldson’s group and coauthor of the study. Young found these glial findings enlightening as they suggest that glia, which are often seen as neurons’ helpers, might have a big role in bond formation between couples.

In neurons, the team also found upregulation of genes associated with the dopaminergic system, which is implicated in the control of reward seeking behaviors but only after the brief separation. “This suggests that there may be some withdrawal process happening, some motivational aspect or some frustration resulting from wanting to be with the partner and not being able to,” said Donaldson.

See “Animal Divorce: When and Why Pairs Break Up

According to Young, one limitation of the study is that the researchers cannot differentiate the types of cells in which these gene expression changes happened as they used a bulk RNA-seq instead of single cell sequencing. He also pointed out that looking at other brain regions connected to the nucleus accumbens is a relevant next step to get a better understanding of pair bond formation and loss at a brain network level.

Donaldson believes that there is still a lot more to learn about the biological basis of grieving and successful adaptation to loss. “There haven’t been many studies, but it is also that societally, we do a really bad job for people when they’re grieving,” she said. “It would be wonderful if, as a society, we got better at sort of learning what loss looks like, what grieving looks like, and how to help those people who are grieving.”

Keywords

Meet the Author

  • Black and white portrait by Mariella Bodemeier Loayza Careaga, PhD

    Mariella Bodemeier Loayza Careaga, PhD

    Mariella is an assistant editor at The Scientist. She has a background in neuroscience, and her work has appeared in Drug Discovery News and Massive Science.

Published In

<em>The Scientist </em>Fall 2023 cover
Fall 2023

Defying Dogma

To understand how memories are formed and maintained, neuroscientists travel far beyond the cell body in search of answers.

Share
You might also be interested in...
Loading Next Article...
You might also be interested in...
Loading Next Article...
3D illustration of a gold lipid nanoparticle with pink nucleic acid inside of it. Purple and teal spikes stick out from the lipid bilayer representing polyethylene glycol.
February 2025, Issue 1

A Nanoparticle Delivery System for Gene Therapy

A reimagined lipid vehicle for nucleic acids could overcome the limitations of current vectors.

View this Issue
Considerations for Cell-Based Assays in Immuno-Oncology Research

Considerations for Cell-Based Assays in Immuno-Oncology Research

Lonza
An illustration of animal and tree silhouettes.

From Water Bears to Grizzly Bears: Unusual Animal Models

Taconic Biosciences
Sex Differences in Neurological Research

Sex Differences in Neurological Research

bit.bio logo
New Frontiers in Vaccine Development

New Frontiers in Vaccine Development

Sino

Products

Tecan Logo

Tecan introduces Veya: bringing digital, scalable automation to labs worldwide

Explore a Concise Guide to Optimizing Viral Transduction

A Visual Guide to Lentiviral Gene Delivery

Takara Bio
Inventia Life Science

Inventia Life Science Launches RASTRUM™ Allegro to Revolutionize High-Throughput 3D Cell Culture for Drug Discovery and Disease Research

An illustration of differently shaped viruses.

Detecting Novel Viruses Using a Comprehensive Enrichment Panel

Twist Bio&nbsp;