Nav: Home

Power up: growing neurons undergo major metabolic shift

July 12, 2016

LA JOLLA--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.

"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.
-end-
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.

Salk Institute

Related Neurons Articles:

A molecule that directs neurons
A research team coordinated by the University of Trento studied a mass of brain cells, the habenula, linked to disorders like autism, schizophrenia and depression.
Shaping the social networks of neurons
Identification of a protein complex that attracts or repels nerve cells during development.
With these neurons, extinguishing fear is its own reward
The same neurons responsible for encoding reward also form new memories to suppress fearful ones, according to new research by scientists at The Picower Institute for Learning and Memory at MIT.
How do we get so many different types of neurons in our brain?
SMU (Southern Methodist University) researchers have discovered another layer of complexity in gene expression, which could help explain how we're able to have so many billions of neurons in our brain.
These neurons affect how much you do, or don't, want to eat
University of Arizona researchers have identified a network of neurons that coordinate with other brain regions to influence eating behaviors.
Mood neurons mature during adolescence
Researchers have discovered a mysterious group of neurons in the amygdala -- a key center for emotional processing in the brain -- that stay in an immature, prenatal developmental state throughout childhood.
Connecting neurons in the brain
Leuven researchers uncover new mechanisms of brain development that determine when, where and how strongly distinct brain cells interconnect.
The salt-craving neurons
Pass the potato chips, please! New research discovers neural circuits that regulate craving and satiation for salty tastes.
When neurons are out of shape, antidepressants may not work
Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed medication for major depressive disorder (MDD), yet scientists still do not understand why the treatment does not work in nearly thirty percent of patients with MDD.
Losing neurons can sometimes not be that bad
Current thinking about Alzheimer's disease is that neuronal cell death in the brain is to blame for the cognitive havoc caused by the disease.
More Neurons News and Neurons Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Reinvention
Change is hard, but it's also an opportunity to discover and reimagine what you thought you knew. From our economy, to music, to even ourselves–this hour TED speakers explore the power of reinvention. Guests include OK Go lead singer Damian Kulash Jr., former college gymnastics coach Valorie Kondos Field, Stockton Mayor Michael Tubbs, and entrepreneur Nick Hanauer.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at Radiolab.org/donate.