To Understand Brain Disorders, Consider the Astrocyte

This was taking a long time. The first couple of years, we worked out the immunopanning and culturing of the astrocytes. One challenge was to make sure that the media didn't have any that would interfere with their measurement. The scientists had to make sure that culturing astrocytes in a petri dish wouldn't change how they acted in the brain.

The scientists looked at the genes they expressed after they established that the cells behaved normally. They looked at those to normal cells. Across all three disorder models, they found approximately 11 genes that were up regulated.

The two were not always in sync. One might think that an increase in a gene's expression would correlate with an increase in theProtein associated with it There wasn't much overlap between genes that were overexpressed and the ones that were overproduced. Allen says that it highlights that you need to look at more than just genes.

The lack of overlap is a "striking" result according to Baldwin. She says that the only thing that can be captured by sequencing is all the regulation that occurs when the product is made. She says that decoding tells you which genes are available, but doesn't tell you which genes are being turned into something.

Allen's team focused on a few specific proteins that spiked across all three disorder models. IGF is a hormone that helps in brain development and one of the reasons it is called Igfbp2. Allen said that the idea was that too much of the inhibitor was being made by the astrocytes. The lab was trying to suppress it. They gave living mice with Rett's syndrome an antidote and found that their brain cells grew normally.

Bmp6 was produced in all three animal models. It is thought to regulate the growth of the immune system. The team tried to find out what happened when they turned theprotein down. They put the mouse neurons in a dish and added the astrocytes from the mice. The tendrils grew when the scientists tried again. The production of Bmp6 seemed to be knocked out.

Allen says that turning up Bmp6 may also turn up Igfbp2, which could lead to some of the deficits.