Looking for patterns in the brain

Where exactly are hormones active in our brain and which genes are involved? Delft researchers and colleagues from Leiden University Medical Center developed a technique that should lead to new insights quickly.

image: Wikipedia
image: Wikipedia

Ever wondered what exactly happens in your brain when you get stressed out? You are not the only one in the blur. Scientists have only vague clues. The stress hormone cortisol stirs things up in your head. But the exact chain of reactions that this hormone, or any hormone for that matter, sets in motion, is still largely a mystery.

Whether it is the cognitive function, mood or behaviour; hormones are into play. They are the conductors of a huge biochemical orchestra involving myriads of genes. Many of which are unknown. To better understand the function of hormones in the brain, these genes, and the areas in the brain where they are active, need to be discovered.

A team of researchers at TU Delft and Leiden University Medical Center believes it has found a way to accelerate this process. In a publication in PNAS that appeared earlier this week, the scientists describe how they unleashed some serious data mining on a huge pile of information; all the records of the activity of 20,000 genes in the mouse brain. This dataset is called the Allen Brain Atlas, and it is a freely available online dataset.

The researchers looked for correlations between genes associated with the receptors for steroid hormones and other genes that respond to these hormones. And they found interesting patterns. Cortisol, for instance, interacts with a different set of genes in the hippocampus than it does in the hypothalamus.

"With this technique we can map brain circuits," explained endocrinologist Dr. Onno Meijer (LUMC). "It allows us to investigate the role of hormones in many different parts of the brain at the same time. Steroid hormone receptors act like switches. They decide what compounds a cell will produce after being activated by a hormone. Depending on their location in the brain, cells contain different sets of these active genes."

Ahmed Mahfouz, of the Pattern Recognition and Bioinformatics group at TU Delft, who is the first author of the publication 'Genome-wide coexpression of steroid receptors in the mouse brain', believes this search method in the Brain Atlas opens up many novel research opportunities. "We have shown that we can discover genes associated with hormones in the brain without dissecting mouse brains." The method is thus much less laborious, it is quicker, cheaper and more animal-friendly.

The researchers made another interesting discovery. They saw that oestrogen and cortisol are both able to control several areas in the brain at the same time, whereas dopamine-rich areas are very selectively sensitive to cortisol and testosterone. "These are all useful insights which we can largely transfer to the human brain," said Meijer. "In the future, we hope also to apply our method of data analysis to data from the human brain."

The Allen Brain Atlas was created by a brain institute in Seattle using hundreds of millions of dollars of financial support from Paul Allen (co-founder of Microsoft). The atlas contains detailed data on the activity of 20,000 genes throughout the mouse brain. In the Atlas, the brain is divided into 60,000 blocks measuring 200 by 200 micrometres.

The research was carried out as part of the STW Genes in Space project in the LUMC Radiology and Endocrinology departments, the Erasmus MC Endocrinology department, and the Pattern Recognition and Bioinformatics group at TU Delft.