In old animals, three days on a highly processed diet lacking fiber – nutritionally similar to a hotdog on a white-flour bun – was linked to cellular and behavioral signs of cognitive problems traced to the emotional memory center of the brain.
Photo Credit: Kelsey Todd
Scientific Frontline: "At a Glance" Summary
- Main Discovery: Consuming a highly processed, fiber-deficient diet for just three days impairs emotional memory governed by the amygdala in aged brains, causing rapid cognitive and cellular dysfunction regardless of fat or sugar levels.
- Methodology: Researchers fed young and aged male rats either normal chow or one of five refined diets with varying fat and sugar combinations, all lacking fiber, for three days. They then conducted behavioral tests and analyzed gut microbiomes, blood samples, and the mitochondria of brain cells.
- Key Data: All fiber-deficient experimental diets resulted in impaired amygdala-based emotional memory in aged rats and caused a significant reduction in the anti-inflammatory gut molecule butyrate. Hippocampus-related memory was negatively affected solely by the high-fat, low-sugar diet.
- Significance: The rapid vulnerability of the amygdala to refined, low-fiber diets highlights a dietary mechanism for cognitive decline in older adults. This impairment disrupts risk assessment, potentially increasing susceptibility to physical danger, financial exploitation, and scams, and occurs well before diet-induced obesity.
- Future Application: Dietary fiber interventions or direct butyrate supplementation could be developed as targeted preventative or restorative treatments to combat age-related cognitive impairment and regulate brain inflammation associated with poor nutrition.
- Branch of Science: Neuroscience, Nutritional Science, and Immunology.
- Additional Detail: Cellular analysis revealed that the mitochondria within the brain's microglia in aged rats exhibited depressed respiration and failed to adapt to energy demands when exposed to the refined diets, an adaptation failure not seen in younger brains.
Past studies in animals have shown that a highly processed diet is linked to memory problems and inflammation in the aged brain – and the effect can happen fast, after just three days of poor eating.
A new study suggests another dietary pitfall could have a similar damaging effect in a similarly short amount of time in older adults: a lack of fiber.
The study in rats also points to the amygdala – the small structure governing emotional memories, especially related to bad experiences – as a brain region that is particularly sensitive to a highly processed diet. Every type of refined diet fed to old animals was associated with cellular and behavioral signs of cognitive problems traced to this emotional memory center of the brain.
“The amygdala is important for learning the association between something fearful and a bad outcome. And we found that all of the refined diets, whether they were high fat, high sugar, low fat, low sugar, it didn’t matter. They all impaired memory that’s governed by the amygdala,” said co-lead author Ruth Barrientos, an investigator in the Institute of Brain, Behavior and Immunology at The Ohio State University.
“And when we looked to see the common thread among all of those diets, the one thing that became very obvious was that they all lack fiber.”
Not learning the association between an action and its outcome, especially when it’s dangerous or risky, may increase the risk for physical or financial harm, said Barrientos, also an associate professor of psychiatry and behavioral health and neuroscience in Ohio State’s College of Medicine.
“The amygdala plays a role in that kind of awareness and learning,” she said. “Its vulnerability to a refined diet is therefore concerning for older adults who are at greater risk of financial exploitation and scams.”
The research was published recently in the journal Brain, Behavior, and Immunity.
Barrientos has studied the effects of high-fat and highly processed diets on the aged brain for several years, seeing behavioral results and related indications of inflammation in both the amygdala and the hippocampus, which is important for spatial, autobiographical and episodic memory.
In this work, she and colleagues focused on disentangling the diet contents to see whether fat or sugar, or something else, had the strongest link to cognitive impairment in rats.
Young and aged male rats were fed either normal chow or one of five experimental diets for three days: low fat, low sugar; low fat, high sugar; medium fat, low sugar; medium fat, high sugar; or high fat, low sugar.
Behavioral tests showed that old animals that were fed all of the refined diets – no matter the level of fat or sugar – had impaired long-term emotional memory based in the amygdala compared to young rats on the same diets. In contrast, memory-related behavior traced to the hippocampus was negatively affected only by the high-fat, low-sugar diet.
And then there was the no-fiber factor. All of the experimental diets lacked fiber, and examination of the rats’ guts and blood showed a significant reduction in a key molecule, called butyrate, that is produced in the gut and circulated in the blood when dietary fiber is broken down by gut microbes.
Previous research by other labs has shown that butyrate has anti-inflammatory effects and can cross the blood-brain barrier, which may mean a deficiency in butyrate caused by a lack of dietary fiber could be linked to unregulated inflammation in the brain, Barrientos said.
“What our study really brings to light is the complexity of diet and how it affects so many different things, even the brain,” said co-lead author Kedryn Baskin, assistant professor of physiology and cell biology at Ohio State. “There’s not a magic bullet, but in this case, low butyrate, as a result of a lack of fiber, is a culprit.”
At the cellular level, the researchers found the most compelling evidence of refined diet-related damage in the mitochondria of microglia, cells that have multiple functions important to memory function. When exposed to experimental energy demands in cell cultures, mitochondria from young brains could adapt to the changes, but these power centers in aged brain cells were not able to rise to the challenge.
“The mitochondria are still functioning, but they’re showing depressed respiration and are functioning at a much, much lower rate in the aged compared to the young,” Baskin said.
Though the refined diets caused some weight gain, Barrientos said the findings put to rest the notion that obesity brought on by a highly processed diet is the primary driver of impaired cognition.
“These effects on the brain after you eat something are pretty rapid,” she said. “You can experience this unhealthy cognitive dysfunction well before you reach obesity.”
And while she and Baskin said the data imply increasing fiber in the diet could be beneficial to the brain, the team plans to study whether fiber or butyrate supplementation in animals could reverse the age-related cognitive problems that follow poor eating.
Funding: This work was supported by the National Institute on Aging, the National Center for Advancing Translational Sciences, the Foods for Health Research Initiative at Ohio State, and the National Heart, Lung, and Blood Institute.
Published in journal: Brain, Behavior, and Immunity
Authors: Michael J. Butler a , Jade A. Blackwell a 1 , Andrew A. Sanchez a 1 , Hannah F. Sanders b , Dominic W. Kolonay b , Jeferson Jantsch a c , Stephanie M. Muscat a , Maria Elisa Caetano-Silva d , Akriti Shrestha d , Casey Kin Yun Lim d , Sabrina E. Mackey-Alfonso a , Bryan D. Alvarez a , Robert H. McCusker d, Jacob M. Allen d , Kedryn K. Baskin b , Ruth M. Barrientos
Source/Credit: Ohio State University | Emily Caldwell
Reference Number: ns021926_02