{"id":10424,"date":"2016-07-12T09:53:05","date_gmt":"2016-07-12T16:53:05","guid":{"rendered":"https:\/\/vermont.salk.edu\/?post_type=disclosure&p=10424"},"modified":"2024-01-30T15:20:32","modified_gmt":"2024-01-30T23:20:32","slug":"power-up-growing-neurons-undergo-major-metabolic-shift","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/zh\/news-release\/power-up-growing-neurons-undergo-major-metabolic-shift\/","title":{"rendered":"Power up: growing neurons undergo major metabolic shift"},"content":{"rendered":"

LA JOLLA\u2014Our 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.<\/p>\n

The findings, published July 12 in the journal eLife<\/em><\/a>, reveal a metabolic route thought to go awry in cancer and neurodegenerative diseases, such as Alzheimer\u2019s and Parkinson\u2019s disease<\/a>.<\/p>\n

\u201cThere is relatively little understanding about how neuron metabolism is first established,\u201d says co-senior author Tony Hunter<\/a>, holder of the Renato Dulbecco Chair and American Cancer Society Professor in Salk\u2019s Molecular and Cell Biology Laboratory. \u201cAside from enabling us to understand this process during neuronal development, the work also allows us to better understand neurodegenerative disease.\u201d<\/p>\n

\"figure-4C\"
A key metabolic pathway must be switched off during neuron development, or else\u2014as is shown on the right\u2014fewer neurons (green) survive. The red cells are non\u2013neural cells called glia.<\/p>\n

Click here<\/a> for a high-resolution image<\/p>\n

Credit: Salk Institute<\/figcaption><\/figure>\n

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\u2019s glucose supply. The cell\u2019s 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.<\/p>\n

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. \u201cWe assume that the metabolic shift we describe in this new study happens every time a progenitor cell turns into a neuron,\u201d says the study\u2019s first author Xinde Zheng, a Salk research associate.<\/p>\n

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.<\/p>\n

Hunter, Zheng, Salk\u2019s 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<\/a>. 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.<\/p>\n

In the new study, Hunter\u2019s 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.<\/p>\n

Most surprising is that developing neurons must completely shut down glycolysis, says Hunter. When the researchers prevented that from happening, the neurons quickly died.<\/p>\n

\"Tony-Hunter-Rusty-Gage\"
Tony Hunter and Rusty Gage<\/p>\n

Click here<\/a> for a high-resolution image<\/p>\n

Credit: Salk Institute<\/figcaption><\/figure>\n

\u201cThis 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,\u201d says co-senior investigator \u9c81\u65af\u8482\u00b7\u76d6\u5947<\/a>, a professor in Salk\u2019s Laboratory of Genetics and holder of the Vi and John Adler Chair for Research on Age-Related Neurodegenerative Diseases.<\/p>\n

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\u2019s disease, and different types of neurons to compare any finer differences in metabolism.<\/p>\n

Other authors on the study are Mingji Jin, Jerome Mertens, Yongsung Kim, Li Ma, Li Ma, and Michael Hamm, all of the Salk Institute.<\/p>\n

The research was supported by the National Institutes of Health<\/a>, the G. Harold and Leila Y. Mathers Charitable Foundation<\/a>, the JPB Foundation<\/a>, the Leona M. and Harry B. Helmsley Charitable Trust<\/a>, Annette Merle-Smith, the California Institute for Regenerative Medicine<\/a>, and the Helmsley Center for Genomic Medicine<\/a>.<\/p>","protected":false},"featured_media":10425,"template":"","faculty":[76,72],"disease-research":[124],"class_list":["post-10424","disclosure","type-disclosure","status-publish","has-post-thumbnail","hentry","faculty-rusty-gage","faculty-tony-hunter","disease-research-neuroscience-and-neurological-disorders"],"acf":[],"yoast_head":"\nPower up: growing neurons undergo major metabolic shift - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/zh\/news-release\/power-up-growing-neurons-undergo-major-metabolic-shift\/\" \/>\n<meta property=\"og:locale\" content=\"zh_CN\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Power up: growing neurons undergo major metabolic shift - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA\u2014Our brains can survive only for a few minutes without oxygen. 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