Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Power up: growing neurons undergo major metabolic shift

13.07.2016

Our brains can survive only for a few minutes without oxygen. Salk Institute researchers have now identified the timing of a dramatic metabolic shift in developing neurons, which makes them become dependent on oxygen as a source of energy.

The findings, published July 12 in the journal eLife reveal a metabolic route thought to go awry in cancer and neurodegenerative diseases, such as Alzheimer's and Parkinson's disease.


Salk Institute researchers have now identified the timing of a dramatic metabolic shift in developing neurons, which makes them become dependent on oxygen as a source of energy. A key metabolic pathway must be switched off during neuron development, or else -- as is shown on the right -- fewer neurons (green) survive. The red cells are non-neural cells called glia.

Credit: Salk Institute

"There is relatively little understanding about how neuron metabolism is first established," says co-senior author Tony Hunter, holder of the Renato Dulbecco Chair and American Cancer Society Professor in Salk's Molecular and Cell Biology Laboratory. "Aside from enabling us to understand this process during neuronal development, the work also allows us to better understand neurodegenerative disease."

To send messages along neurons is energetically demanding, and the brain uses both oxygen and glucose intensely. The brain, for example, uses 20 percent of the body's glucose supply. The cell's energy-producing factories, called mitochondria, are scattered throughout the long, slender axons of neurons in order to provide all parts of the cell with a constant supply of energy. As the neurons get bigger, so do the number of mitochondria, according to the new study.

We make new neurons in the womb, and this process continues after birth. Even a few areas in the adult brain continue to make new neurons throughout life. "We assume that the metabolic shift we describe in this new study happens every time a progenitor cell turns into a neuron," says the study's first author Xinde Zheng, a Salk research associate.

The cells that eventually become neurons initially use a pathway called glycolysis, which is a major energy-producing process that takes place in the cytoplasm of the cell and turns glucose into energy in the form of adenosine triphosphate (ATP). At some point, however, the cells switch to a more efficient pathway called oxidative phosphorylation, a process that uses oxygen to produce ATP and occurs inside the mitochondria.

Hunter, Zheng, Salk's Leah Boyer and colleagues previously studied a rare metabolic disease called Leigh syndrome and recently published work showing that less ATP is produced in afflicted neurons. In the process of understanding that disease, they needed to recreate it in a dish, using cells with mutations in the DNA contained within mitochondria. But the team realized that it was not well understood how normally dividing cells generate energy while they divide and differentiate into new cell types.

In the new study, Hunter's team found that as a neuron precursor cell becomes a neuron, genes coding for key metabolic enzymes used in glycolysis switch off their expression,. Those changes work hand in hand to shut down glycolysis. All the while, key regulators of oxidative phosphorylation are ramping up.

Most surprising is that developing neurons must completely shut down glycolysis, says Hunter. When the researchers prevented that from happening, the neurons quickly died.

"This is the first comprehensive analysis of metabolic changes during neuronal differentiation, and the surprising reliance of neurons on oxidative phosphorylation for their sole energy source has clear implications for neuronal vulnerability with age," says co-senior investigator Rusty Gage, a professor in Salk's Laboratory of Genetics and holder of the Vi and John Adler Chair for Research on Age-Related Neurodegenerative Diseases.

The group plans to look more closely at how the metabolic genes are controlled in developing cells. They also plan to study neurons harboring energy defects associated with disease, such as Parkinson's disease, and different types of neurons to compare any finer differences in metabolism.

###

Other authors on the study are Mingji Jin, Jerome Mertens, Yongsung Kim, Li Ma, Li Ma, and Michael Hamm, all of the Salk Institute.

The research was supported by the National Institutes of Health, the G. Harold and Leila Y. Mathers Charitable Foundation, the JPB Foundation, the Leona M. and Harry B. Helmsley Charitable Trust, Annette Merle-Smith, the California Institute for Regenerative Medicine, and the Helmsley Center for Genomic Medicine.

About the Salk Institute for Biological Studies:

Every cure has a starting point. The Salk Institute embodies Jonas Salk's mission to dare to make dreams into reality. Its internationally renowned and award-winning scientists explore the very foundations of life, seeking new understandings in neuroscience, genetics, immunology and more. The Institute is an independent nonprofit organization and architectural landmark: small by choice, intimate by nature and fearless in the face of any challenge. Be it cancer or Alzheimer's, aging or diabetes, Salk is where cures begin. Learn more at: salk.edu.

Media Contact

Salk Communications
press@salk.edu
858-453-4100

 @salkinstitute

http://www.salk.edu 

Salk Communications | EurekAlert!

More articles from Life Sciences:

nachricht Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory

nachricht How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>