Featured Research

from universities, journals, and other organizations

Dual role of brain glycogen revealed by researchers

Date:
February 27, 2014
Source:
Institute for Research in Biomedicine (IRB Barcelona)
Summary:
Key questions regarding the activity of glycogen in neurons are answered in two recently published articles, building on years of research and publications. The authors postulated that glycogen is a lifeguard under oxygen depletion, a condition that leads the brains to shut down and that often occurs at birth and in cerebral infarctions in adults, which leads to severe consequences, such a cerebral paralysis. Their results are the first evidence that neurons constantly store glycogen by accumulating small amounts and using it as quickly as it becomes available. The beneficial and toxic roles of brain glycogen continue to be the main focus on ongoing research.

In 2007, in an article published in Nature Neuroscience, scientists at the Institute for Research in Biomedicine (IRB Barcelona) headed by Joan Guinovart, an authority on glycogen metabolism, reported that in Lafora Disease (LD), a rare and fatal neurodegenerative condition that affects adolescents, neurons die as a result of the accumulation of glycogen -- chains of glucose. They went on to propose that this accumulation is the root cause of this disease.

The breakthrough of this paper was two-sided: first, the researchers established a possible cause of LD and therefore were able to point to a plausible therapeutic target, and second, they discovered that neurons have the capacity to store glycogen -- an observation that had never been made -- and that this accumulation was toxic.

Some scientists sceptical about the article upheld that the glycogen deposits were not cause by the neurodegeneration but were a consequence of another, more important, cell imbalance, such as a down deregulation of autophagy -- the cell recycling and cleaning programme. In several articles, Guinovart's "Metabolic engineering and diabetes therapy" group has recently brought to light evidence of the toxicity of glycogen deposits for LD patients, and has now provided irrefutable data.

In an article published at the beginning of February in Human Molecular Genetics, with the associate researcher Jordi Duran as first author, the scientists show that in LD the accumulation of glycogen directly causes neuronal death and triggers cell imbalances such a decrease in autophagy and synaptic failure. All these alterations lead to the symptoms of LD, such as epilepsy.

Glycogen, a Trojan horse for neurons?

There was still a greater mystery to be solved. Was glycogen synthase truly a Trojan horse for neurons, as apparently established in the article in Nature Neuroscience? That is to say, was the accumulation of glycogen always fatal for cells, thus explaining why their glycogen synthesis machinery is silenced? The inevitable question was then why these cells had such machinery.

In another paper published in Journal of Cerebral Blood Flow & Metabolism, part of the Nature Group, the researchers provided the first evidence that neurons constantly store glycogen but in a different way: accumulating small amounts and using it as quickly as it becomes available. In this regard, the scientists set up new, more sensitive, analytical techniques to confirm that the machinery responsible for glycogen synthesis and degradation existed. In summary, they showed that, in small amounts, glycogen is beneficial for neurons.

"For example, while the liver accumulates glycogen in large amounts and releases it slowly to maintain blood sugar levels, above all when we sleep, neurons synthesize and degrade small amounts of this polysaccharide continuously. They do not use it as an energy store but as a rapid and small, but constant, source of energy," explains Guinovart, also senior professor at the University of Barcelona (UB).

To observe the action of glycogen, the scientists forced cultured mouse neurons to survive under oxygen depletion. They demonstrated that the first cells to die were those in which the capacity to synthesise glycogen had been removed. The same experiments were performed in collaboration with Marco Milán's "Development and growth control" group in the in vivo model of the fruit fly Drosophila melanogaster. These tests led to the same conclusions.

The researchers postulated that glycogen is a lifeguard under oxygen depletion, a condition that leads the brains to shut down and that often occurs at birth and in cerebral infarctions in adults, which leads to severe consequences, such a cerebral paralysis.

"It is the first function of glycogen that we have discovered in neurons, but we still have to identify its function in normal conditions and establish how the mechanism works," says Jordi Duran. Postdoctoral researcher Isabel Saez is the first author of the article out today, which involved the collaboration of ICREA Research Professor Marco Milán's lab.

The beneficial and toxic roles of brain glycogen are currently the focus of main research lines conducted by Joan Guinovart's lab.


Story Source:

The above story is based on materials provided by Institute for Research in Biomedicine (IRB Barcelona). Note: Materials may be edited for content and length.


Journal References:

  1. J. Duran, A. Gruart, M. Garcia-Rocha, J. M. Delgado-Garcia, J. J. Guinovart. Glycogen accumulation underlies neurodegeneration and autophagy impairment in Lafora disease. Human Molecular Genetics, 2014; DOI: 10.1093/hmg/ddu024
  2. Isabel Saez, Jordi Duran, Christopher Sinadinos, Antoni Beltran, Oscar Yanes, María F Tevy, Carlos Martínez-Pons, Marco Milán, Joan J Guinovart. Neurons have an active glycogen metabolism that contributes to tolerance to hypoxia. Journal of Cerebral Blood Flow & Metabolism, 2014; DOI: 10.1038/jcbfm.2014.33

Cite This Page:

Institute for Research in Biomedicine (IRB Barcelona). "Dual role of brain glycogen revealed by researchers." ScienceDaily. ScienceDaily, 27 February 2014. <www.sciencedaily.com/releases/2014/02/140227142611.htm>.
Institute for Research in Biomedicine (IRB Barcelona). (2014, February 27). Dual role of brain glycogen revealed by researchers. ScienceDaily. Retrieved September 23, 2014 from www.sciencedaily.com/releases/2014/02/140227142611.htm
Institute for Research in Biomedicine (IRB Barcelona). "Dual role of brain glycogen revealed by researchers." ScienceDaily. www.sciencedaily.com/releases/2014/02/140227142611.htm (accessed September 23, 2014).

Share This



More Health & Medicine News

Tuesday, September 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Liberia Pleads for Help to Fight Ebola

Liberia Pleads for Help to Fight Ebola

AP (Sep. 22, 2014) — Liberia's finance minister is urging the international community to quickly follow through on pledges of cash to battle Ebola. Bodies are piling up in the capital Monrovia as the nation awaits more help. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Ebola Doctor Says Border Controls Critical

Ebola Doctor Says Border Controls Critical

AP (Sep. 22, 2014) — A Florida doctor who helped fight the expanding Ebola outbreak in West Africa says the disease can be stopped, but only if nations quickly step up their response and make border control a priority. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Global Ebola Aid Increasing But Critics Say It's Late

Global Ebola Aid Increasing But Critics Say It's Late

Newsy (Sep. 21, 2014) — More than 100 tons of medical supplies were sent to West Africa on Saturday, but aid workers say the global response is still sluggish. Video provided by Newsy
Powered by NewsLook.com
Sierra Leone in Lockdown to Control Ebola

Sierra Leone in Lockdown to Control Ebola

AP (Sep. 21, 2014) — Sierra Leone residents remained in lockdown on Saturday as part of a massive effort to confine millions of people to their homes in a bid to stem the biggest Ebola outbreak in history. (Sept. 20) Video provided by AP
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:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

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