Posts tagged aerobic glycolysis
Articles and news from the latest research reports.
Researchers boost insect aggression by altering brain metabolism
Scientists report they can crank up insect aggression simply by interfering with a basic metabolic pathway in the insect brain. Their study, of fruit flies and honey bees, shows a direct, causal link between brain metabolism (how the brain generates the energy it needs to function) and aggression.
The team reports its findings in the Proceedings of the National Academy of Sciences.
The new research follows up on previous work from the laboratory of University of Illinois entomology professor and Institute for Genomic Biology director Gene Robinson, who also led the new analysis. When he and his colleagues looked at brain gene activity in honey bees after they had faced down an intruder, the team found that some metabolic genes were suppressed. These genes play a key role in the most efficient type of energy generation in cells, a process called oxidative phosphorylation.
“It was a counterintuitive finding because these genes were down-regulated,” Robinson said. “You tend to think of aggression as requiring more energy, not less.”
In the new study, postdoctoral researcher Clare Rittschof used drugs to suppress key steps in oxidative phosphorylation in the bee brains. She saw that aggression increased in the drugged bees in a dose-responsive manner, Robinson said. But the drugs had no effect on chronically stressed bees – they were not able to increase their aggression in response to an intruder.
“Something about chronic stress changed their response to the drug, which is a fascinating finding in and of itself,” Robinson said. “We want to know just how this experience gets under their skin to affect their brain.”
In separate experiments, postdoctoral researcher Hongmei Li-Byarlay and undergraduate student Jonathan Massey found that reduced oxidative phosphorylation in fruit flies also increased aggression. Using advanced fly genetics, the team found this effect only when oxidative phosphorylation was reduced in neurons, but not in neighboring cells known as glia. This finding, too, was surprising, since “glia are metabolically very active, and are the energy storehouses of the brain,” Robinson said.
The findings offer insight into the immediate and longer-term changes that occur in response to threats, Robinson said.
“When an animal faces a threat, it has an immediate aggressive response, within seconds,” Robinson said. But changes in brain metabolism take much longer and cannot account for this immediate response, he said. Such changes likely make individuals more vigilant to subsequent threats.
“This makes good sense in an ecological sense,” Robinson said, “because threats often come in bunches.”
The fact that the researchers observed these effects in two species that diverged 300 million years ago makes the findings even more compelling, Robinson said.
“Because fruit flies and honey bees are separated by 300 million years of evolution, this is a very robust and well-conserved mechanism.”
Sugar-burning in the adult human brain is associated with continued growth, and remodeling
Although brain growth slows as individuals age, some regions of the brain continue to develop for longer than others, creating new connections and remodeling existing circuitry. How this happens is a key question in neuroscience, with implications for brain health and neurodegenerative diseases. New research published today shows that those areas of the adult brain that consume more fuel than scientists might expect also share key characteristics with the developing brain. Two Allen Brain Atlas resources – the Allen Human Brain Atlas and the BrainSpan Atlas of the Developing Human Brain – were crucial to uncovering the significance of these sugar-hungry regions. The results are published this month in the journal Cell Metabolism.
"These experiments and analysis represent the first union of its kind between functional imaging data and a biological mechanism, with the Allen Brain Atlas resources helping to bridge that gap," comments Michael Hawrylycz, Ph.D., Investigator with the Allen Institute for Brain Science and co-author of the study. Data from PET scans provides structural insight into the brain, but until now, has not been able to elucidate function. "Now we can make the comparison between the functional data and the gene expression data," says Hawrylycz, "so instead of just the ‘where,’ we now also have the ‘what’ and ‘how.’"
The brain needs to constantly metabolize fuel in order to keep running, most often in the form of glycolysis: the breaking down of stored sugar into useable energy. PET scans of the brain, which illuminate regions consuming sugar, show that some select areas of the brain seemed to exhibit fuel consumption above and beyond what was needed for basic functioning. In cancer biology, this same well-known phenomenon of consuming extra fuel—called “aerobic glycolysis”—is thought to provide support pathways for cell proliferation. In the brain, aerobic glycolysis is dramatically increased during childhood and accounts for as much as one third of total brain glucose consumption at its peak around 5 years of age, which is also the peak of synapse development.
Since aerobic glycolysis varies by region of the brain, Hawrylycz and co-author Marcus Raichle, Ph.D., at Washington University in St. Louis, wondered whether regions of the brain with higher levels of aerobic glycolysis might be associated with equivalent growth processes, like synapse formation. If so, this would point to aerobic glycolysis as a reflection of “neoteny,” or persistent brain development like the kind that takes place during early childhood.
In order to delve into the significance of aerobic glycolysis, researchers examined the genes expressed at high levels in those regions where aerobic glycolysis was taking place. The team identified 16 regions of the brain with elevated levels of aerobic glycolysis and ranked their neotenous characteristics. True to prediction, they found that gene expression data from those 16 regions suggested highly neotenous behavior.
The next phase was to identify which genes were specifically correlated with aerobic glycolysis in those regions. The Allen Brain Atlas resources proved crucial in this task, helping to pinpoint gene expression in different regions at various points in development. The Allen Human Brain Atlas was used to investigate the adult human brain, while the BrainSpan Atlas of the Developing Human Brain, developed by a consortium of partners and funded by the National Institutes of Health, provided a window into how gene expression changes as the brain ages.
Analysis of the roles of those genes pointed clearly towards their roles in growth and development; top genes included those responsible for axon guidance, potassium ion channel development, synaptic transmission and plasticity, and many more. The consistent theme was development, pointing to aerobic glycolysis as a hallmark for neotenous, continually developing regions of the brain.
"Using both the adult and developmental data, we were able to study gene expression at each point in time," describes Hawrylycz. "From there, we were able to see the roles of those genes that were highly expressed in regions with aerobic glycolysis. As it turns out, those genes are consistently involved in the remodeling and maturation process, synaptic growth and neurogenesis—all factors in neoteny." "The regions we identified as being neotenous are areas of the cortex particularly associated with development of intelligence and learning," explains Hawrylycz. "Our results suggest that aerobic glycolysis, or extra fuel consumption, is a marker for regions of the brain that continue to grow and develop in similar ways to the early human brain."
(Source: eurekalert.org)