Ketogenic diet reduces aggression after concussion

Summary: Male fruit flies fed a ketone supplemented diet expressed reduced levels of aggression following concussion than those who were not exposed to the dietary intervention.

Source: University of Connecticut

A high-fat diet reduces male fruit fly aggression after concussions, UConn researchers report in the 30 October issue of Frontiers in Neuroscience. The findings hint at potential treatments to prevent brain damage after head impacts.

Concussions became big news when National Football League players successfully sued the league over claims that repeated head impacts from playing professional football had permanently damaged their brains. It quickly became apparent that athletes in other sports, both amateur and professional, were also at risk. And despite all we now know about the dangers of concussion, there is no good treatment for it other than to rest and hope the effects are temporary.

“The treatments for concussion are pretty non-existent,” says Derek Lee ’18, ’20 (CLAS), a graduate student in neurobiologist Geoff Tanner’s lab who hails from Tolland, Conn. Lee follows football, and the concussion lawsuits were on his mind when he had the opportunity to start research in Tanner’s lab as an undergraduate.

One of the difficult aspects of studying concussions is that it’s not entirely clear how concussions damage the brain, nor why some damage is permanent and some not. As Lee and Tanner looked into the existing research, they found evidence that concussions might kill brain cells through excito-toxicity. Excito-toxicity means that the cells get over-excited by some injury or event, and use up all their glucose, the sugar they use for energy, too fast; sometimes the cells die.

But glucose isn’t brain cells’ only source of energy; such cells can also run on ketone bodies produced from fats. Evidence from epilepsy research has shows that brain cells that metabolize ketone bodies in addition to or instead of glucose stay calmer, preventing seizures and excito-toxicity. Tanner and Lee thought that perhaps that could help prevent cell death from concussions, too.

Lee and another student, Shane Baldwin ’17 (CLAS), from Southington, Conn., designed an experiment to test the idea in fruit flies. Along with Krishna Vali ’19 (CLAS), from Seymour, Conn., and several other Tanner lab students, they put male fruit flies in a high impact trauma device to simulate repeated traumatic brain injuries. Most of the fruit flies collided with the wall of the vial, and were stunned; previous work had shown this caused injury to the fruit flies’ neurons. The Tanner Lab coined a shorthand for it: Big Adverse Neurotraumatic Generating eventS (BANGS). Essentially, BANGS give the fruit flies traumatic brain injuries similar to human concussions.

In their experiments, the group took a group of male fruit flies, and BANG’d half of them when they were five days old. (That’s equivalent to young adulthood in fruit flies.) Half the flies from each group, those BANG’d and those not, were fed a normal, high carbohydrate fruit fly diet. The other half were fed a diet supplemented with beta-hydroxybutyrate, a ketone body. It was the fruit fly version of the ketogenic diet, an eating regimen used in humans to calm epilepsy and also to lose weight.

This shows a red brain
The team found that male fruit flies who’d been BANG’d were more aggressive with each other when exposed to the body of a female fruit fly than were males without neurotrauma. Image is in the public domain.

The team found that male fruit flies who’d been BANG’d were more aggressive with each other when exposed to the body of a female fruit fly than were males without neurotrauma. The BANG’d males were more likely to flare their wings, rear up on their hind legs, and box with other males than the flies who had not been BANG’d.

However, the BANG’d males who’d eaten the ketone-supplemented diet their whole lives behaved less aggressively, more like males who hadn’t suffered a BANG.

When the researchers altered the experiment so that the flies started eating the high-ketone diet only on day 5 (on the day they were BANG’d), the diet still dampened aggression, suggesting it might work as a treatment, protecting injured brain cells and helping them recover.

Lee’s research for his master’s degree is continuing to focus on fruit flies with neurotrauma, but now looking at differences in protein expression in the flies’ brains. Tanner hopes to expand the work to look at the potential protective effect of a high-ketone diet in female fruit flies as well as males. While more research is needed into how the high-ketone diet works to reduce brain injury-related aggression in flies, it’s a hopeful pointer towards a potential treatment for concussions in humans.

About this neuroscience research article

University of Connecticut
Media Contacts:
Kim Krieger – University of Connecticut
Image Source:
The image is in the public domain.

Original Research: Open access
“Dietary Supplementation With the Ketogenic Diet Metabolite Beta-Hydroxybutyrate Ameliorates Post-TBI Aggression in Young-Adult Male Drosophila”. Geoff Tanner et al.
Frontiers in Neuroscience doi:10.3389/fnins.2019.01140.


Dietary Supplementation With the Ketogenic Diet Metabolite Beta-Hydroxybutyrate Ameliorates Post-TBI Aggression in Young-Adult Male Drosophila

Traumatic brain injury (TBI), caused by repeated concussive head trauma can induce chronic traumatic encephalopathy (CTE), a neurodegenerative disease featuring behavioral symptoms ranging from cognitive deficits to elevated aggression. In a Drosophila model, we used a high-impact trauma device (Katzenberger et al., 2013, 2015) to induce TBI-like symptoms and to study post-TBI behavioral outcomes. Following TBI, aggression in banged male flies was significantly elevated as compared with that in unbanged flies. These increases in aggressive behavior were not the result of basal motility changes, as measured by a negative geotaxis assay. In addition, the increase in post-TBI aggression appeared to be specific to concussive trauma: neither cold exposure nor electric shock—two alternate types of trauma—significantly elevated aggressive behavior in male-male pairs. Various forms of dietary therapy, especially the high-fat, low-carbohydrate ketogenic diet (KD), have recently been explored for a wide variety of neuropathies. We thus hypothesized that putatively neuroprotective dietary interventions might be able to suppress post-traumatic elevations in aggressive behavior in animals subjected to head-trauma-inducing strikes, or “bangs”. We supplemented a normal high-carbohydrate Drosophila diet with the KD metabolite beta-hydroxybutyrate (β-HB)—a ketone body (KB). Banged flies raised on a KB-supplemented diet exhibited a marked reduction in aggression, whereas aggression in unbanged flies was equivalent whether dieted with KB supplements or not. Pharmacological blockade of the ATP-sensitive potassium (KATP) channel abrogated KB effects reducing post-TBI aggression while pharmacological activation mimicked them, suggesting a mechanism by which KBs act in this model. KBs did not significantly extend lifespan in banged flies, but markedly extended lifespan in unbanged flies. We have thus developed a functional model for the study of post-TBI elevations of aggression. Further, we conclude that dietary interventions may be a fruitful avenue for further exploration of treatments for TBI- and CTE-related cognitive-behavioral symptoms.

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