Growth of new brain cells requires 'epigenetic' switch

January 8, 2009

New cells are born every day in the brain's hippocampus, but what controls this birth has remained a mystery. Reporting in the January 1 issue of Science, neuroscientists at the Johns Hopkins University School of Medicine have discovered that the birth of new cells, which depends on brain activity, also depends on a protein that is involved in changing epigenetic marks in the cell's genetic material.

"How is it that when you see someone you met ten years ago, you still recognize them? How do these transient events become long lasting in the brain, and what potential role does the birth of new neurons play in making these memories?" says Hongjun Song, Ph.D., an associate professor of neurology and member of the Johns Hopkins Institute of Cell Engineering's NeuroICE. "We really want to understand how daily life experiences trigger the birth and growth of new neurons, and make long-lasting changes in the brain."

The researchers reasoned that making long-term memories might require long-term changes in brain cells. And one type of cellular change that has long-lasting effects is so-called epigenetic change, which can alter a cell's DNA without changing its sequence but does change how and which genes are turned on or off. So they decided to look at the 40 to 50 genes known to be involved in epigenetics, and see if any of them are turned on in mouse brain cells that have been stimulated with electroconvulsive therapy—shock treatment. "It's long been known that ECT induces neurogenesis in rodents and humans, so we used it as our test case to find what is triggered downstream to cause new cells to grow," says Song.

One gene turned on in response to ECT was Gadd45b, a gene previously implicated in immune system function and misregulated in brain conditions like autism. To confirm Gadd45b is turned up in response to brain activity, the researchers also examined mice experiencing a different activity. Exposure to new surroundings, the team found, also turns on Gadd45b in brain cells.

To find out if Gadd45b is required for new brain-cell growth, the research team made mice lacking the Gadd45b gene and tested their ability to generate new brain cells after ECT. They injected the mice with a dye that marks new cells and three days after ECT examined the number of new cells containing that dye in brains from mice with and without the Gdd45b gene. They found that while normal brains showed a 140 percent increase in cell number after ECT, brains lacking Gadd45b only showed a 40 percent increase.

"The question then was, How does Gadd45b do this?" says Song. "It's been controversial that Gadd45b can promote epigenetic changes like global DNA demethylation, but we show that it can promote demethylation of certain genes."

The chemical methyl group, when attached to DNA near genes, can turn those genes off. This so-called epigenetic change is thought to silence genes a cell doesn't use.

By dissecting mature neurons from normal mouse brains and looking for the presence of methyl groups at certain genes known to promote cell growth, the researchers found that after ECT, these genes became demethylated.

However, doing the same thing with mice lacking Gadd45b resulted in no demethylation, suggesting to the team that Gadd45b is indeed required for demethylation.

"We're really excited about this—it's the first time we've seen dynamic epigenetic DNA changes in response to brain activity," says Song.

"Now that we have the mice lacking Gadd45b, our next goal is to see if these mice have problems with learning and memory and how Gadd45b specifically promotes the demethylation to lead to these long-term changes in the brain."

Source: Johns Hopkins Medical Institutions

Explore further: Caltech biologists discover how T cells make a commitment

Related Stories

Caltech biologists discover how T cells make a commitment

July 2, 2010

( -- When does a cell decide its particular identity? According to biologists at the California Institute of Technology (Caltech), in the case of T cells—immune system cells that help destroy invading pathogens—the ...

Novel Pathway Regulates Timing of Brain-Cell Development

October 5, 2006

Brain formation involves the carefully timed production of different types of nerve cells by neural stem cells: neurons are produced first, then astrocytes. Making too much of one kind of cell and too little of another at ...

When nerve cells can’t make contact

September 22, 2006

Using an animal model, brain researchers in Göttingen have examined the effects of mutations that cause autism in humans. These are mutations in the genes which carry the building instructions for proteins in the neuroligin ...

Scientists find a key culprit in stroke brain cell damage

March 27, 2008

Researchers have identified a key player in the killing of brain cells after a stroke or a seizure. The protein asparagine endopeptidase (AEP) unleashes enzymes that break down brain cells' DNA, scientists at Emory University ...

Major link in brain-obesity puzzle found

January 29, 2007

A single protein in brain cells may act as a linchpin in the body’s weight-regulating system, playing a key role in the flurry of signals that govern fat storage, sugar use, energy balance and weight, University of Michigan ...

Recommended for you

How the finch changes its tune

August 3, 2015

Like top musicians, songbirds train from a young age to weed out errors and trim variability from their songs, ultimately becoming consistent and reliable performers. But as with human musicians, even the best are not machines. ...

Machine Translates Thoughts into Speech in Real Time

December 21, 2009

( -- By implanting an electrode into the brain of a person with locked-in syndrome, scientists have demonstrated how to wirelessly transmit neural signals to a speech synthesizer. The "thought-to-speech" process ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.