Featured Research

from universities, journals, and other organizations

Well-known Enzyme Is Unexpected Contributor To Brain Growth

Date:
March 13, 2009
Source:
Washington University School of Medicine
Summary:
An enzyme researchers have studied for years because of its potential connections to cancer, diabetes, heart disease, hypertension and stroke, appears to have yet another major role to play: helping create and maintain the brain.

An enzyme researchers have studied for years because of its potential connections to cancer, diabetes, heart disease, hypertension and stroke, appears to have yet another major role to play: helping create and maintain the brain.

When scientists at Washington University School of Medicine in St. Louis selectively disabled the enzyme AMP-activated protein kinase (AMPK) in mouse embryos, overall brain size was reduced by 50 percent, the cerebrum and cerebellum were shrunken, and the mice died within three weeks of birth.

Researchers showed that the version of AMPK they disabled was essential to the survival of neural stem cells that create the central nervous system. Many scientists believe these same cells also regularly produce new brain cells essential for learning and memory and the general upkeep of the adult brain.

"For years, scientists have showed how AMPK regulates multiple metabolic processes, and revealed how that influence can affect cancer, diabetes, and many other diseases," says senior author Jeffrey Milbrandt, M.D., Ph.D., the David Clayson Professor of Neurology. "Now, for the first time, we've shown that AMPK can cause lasting changes in cell development. That's very exciting because it opens the possibility of modifying AMPK activity to improve brain function and health."

The study was the featured paper in the February issue of Developmental Cell.

AMPK regulates the energy usage of cells and becomes active when energy resources are low, such as during exercise or times of dietary restriction. Activated AMPK inhibits processes that consume energy, like protein synthesis or fatty acid synthesis, and promotes processes that produce energy, such as the oxidation of fatty acids, the uptake of the sugar glucose, or the creation of mitochondria, which are cellular energy-making units. Activated AMPK also suppresses cell reproduction, an ability that scientists have shown can help shut down the proliferation of some cancer cell lines.

The AMPK enzyme is composed of three subunits called alpha, beta and gamma. The human genome contains genes for two to three versions of each subunit. Until now, the beta unit seemed to be "a boring linker" that merely held the three subunits together, according to Milbrandt.

Instead, Milbrandt and Dasgupta found that the beta subunit was determining where AMPK did its job. AMPK with one version of the subunit, beta 1, was found both in the nucleus of cells and in the body of the cell, which is called the cytoplasm. AMPK with beta 2 was never found in the nucleus—just the cytoplasm.

They showed that when activated AMPK gets into the nucleus of stem cells, it inactivates the retinoblastoma protein, a master regulator of cell reproduction. This allows neural stem cells to survive and proliferate.

"Inhibiting AMPK is something that most cells don't like. It can lead to a variety of consequences, including cell death, but many cell types can tolerate it," says lead author Biplab Dasgupta, Ph.D., research instructor in pathology and immunology. "In contrast, neural stem cells undergo catastrophic cell death in the absence of AMPK containing the beta 1 subunit. We also suspect loss of this form of AMPK may cause severe problems for other stem cells."

Dasgupta calls the new finding particularly interesting given previous connections between AMPK and exercise.

"Exercise activates AMPK and improves cognitive function," says Dasgupta. "Our results suggest brain function may improve because additional activated AMPK makes it easier for adult neural stem cells to reproduce and become new brain cells."

Retinoblastoma, the protein regulated by AMPK in the nucleus, also has less well-defined influence on the ability of stem cells to take on specialized characteristics, and this has Milbrandt intrigued about possible connections between AMPK's new role in stem cells and the long-term health effects of malnutrition during pregnancy. A 1977 study of children born to women starved by the Nazis during World War II suggested that the children had increased risk of heart disease, diabetes, stroke and hypertension.

While these are some of the same disorders that have been linked to AMPK activity in adults, those previous links were made through AMPK's role as a manager of cellular energy usage. Milbrandt wonders if changes in AMPK activity triggered by malnutrition could also be affecting stem cell activity in ways that increase long-term health risks in developing infants.

AMPK's role reversal in stem cells calls for careful use of the enzyme in cancer therapy, the researchers note. Recent studies have shown that stem cells can become cancerous, and in those cancers the researchers now believe it might be better to inhibit AMPK than to activate it. Dasgupta will test this hypothesis on cancer stem cell lines.

Milbrandt plans to learn more about how production of different forms of AMPK is regulated.

"Manipulating this regulation may enable us encourage the development of new brain cells," he says. "We might use that not only to treat medical conditions where brain development is hampered but also to improve cognitive function generally."

Dasgupta B and Milbrandt J. AMP-activated protein kinas phsophorylates retinoblastoma protein to control mammalian brain development. Developmental Cell, February 2009.


Story Source:

The above story is based on materials provided by Washington University School of Medicine. Note: Materials may be edited for content and length.


Cite This Page:

Washington University School of Medicine. "Well-known Enzyme Is Unexpected Contributor To Brain Growth." ScienceDaily. ScienceDaily, 13 March 2009. <www.sciencedaily.com/releases/2009/03/090312092436.htm>.
Washington University School of Medicine. (2009, March 13). Well-known Enzyme Is Unexpected Contributor To Brain Growth. ScienceDaily. Retrieved September 2, 2014 from www.sciencedaily.com/releases/2009/03/090312092436.htm
Washington University School of Medicine. "Well-known Enzyme Is Unexpected Contributor To Brain Growth." ScienceDaily. www.sciencedaily.com/releases/2009/03/090312092436.htm (accessed September 2, 2014).

Share This




More Health & Medicine News

Tuesday, September 2, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Snack Attack: Study Says Action Movies Make You Snack More

Snack Attack: Study Says Action Movies Make You Snack More

Newsy (Sep. 2, 2014) You're more likely to gain weight while watching action flicks than you are watching other types of programming, says a new study published in JAMA. Video provided by Newsy
Powered by NewsLook.com
U.N. Says Ebola Travel Restrictions Will Cause Food Shortage

U.N. Says Ebola Travel Restrictions Will Cause Food Shortage

Newsy (Sep. 2, 2014) The U.N. says the problem is two-fold — quarantine zones and travel restrictions are limiting the movement of both people and food. Video provided by Newsy
Powered by NewsLook.com
Get on Your Bike! London Cycling Popularity Soars Despite Danger

Get on Your Bike! London Cycling Popularity Soars Despite Danger

AFP (Sep. 1, 2014) Wedged between buses, lorries and cars, cycling in London isn't for the faint hearted. Nevertheless the number of people choosing to bike in the British capital has doubled over the past 15 years. Duration: 02:27 Video provided by AFP
Powered by NewsLook.com
Can You Train Your Brain To Eat Healthy?

Can You Train Your Brain To Eat Healthy?

Newsy (Sep. 1, 2014) New research says if you condition yourself to eat healthy foods, eventually you'll crave them instead of junk food. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins