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Powering up: growing neurons make an energy jump
The findings, published in the journal eLife, reveal a metabolic route we think can also go wrong in cancer and neurodegenerative diseases, such as Alzheimer's and Parkinson's.
To send messages along neurons is energetically demanding, and the brain uses both oxygen and glucose intensely. For example, the brain uses 20 percent of the body's glucose (sugar) supply. A cell also has energy-producing factories, called mitochondria, scattered throughout the long, slender axons of neurons. Mitochondria provide all parts of the neuron with a constant supply of energy. As neurons get bigger, so grows the number of mitochondria, according to the new study.
We make new neurons in the womb, a process which continues after birth. 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, research associate in the Cell Biology Laboratory at Salk Institute.
Hunter, Zheng, Salk's Leah Boyer and other colleagues had previously studied a rare metabolic disease called Leigh syndrome, recently publishing work showing that less ATP is produced in Leigh's afflicted neurons.
In this study, Hunter's team saw that as a pre-neuron cell is becomming a neuron, genes coding for glycolysis switch off at the same time as key regulators of oxidative phosphorylation start up.
"This is the first comprehensive analysis of metabolic changes during neuronal differentiation. The surprising reliance of neurons on oxidative phosphorylation for their sole energy source has clear implications for neuronal vulnerability with age," explains 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.
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 research has identified a dramatic metabolic shift in developing neurons.
Neurons become dependent on oxygen for energy after a key metabolic pathway is turned off.
As shown on the right, few GREEN neurons survive. RED cells are non-neural cells called glia..
Image Credit: Salk Institute