Inside Neuroscience: Studies Explore How Diet Affects Brain Structure, Function
The number of people worldwide who are overweight or obese is a growing concern, given the implications for health and wellness on a global scale. According to the most recent reports by the World Health Organization, more than 1.4 billion adults worldwide are overweight and 500 million are obese. Obesity is a major risk factor for a variety of diseases, including some that affect the brain, such as dementia and stroke.
“What we eat really affects our brain, our behavior, our neural circuits, and our health in many ways,” said Ralph DiLeone, associate professor of psychiatry and neurobiology at Yale University and moderator for a press conference on diet and the brain at Neuroscience 2014. During the event, presenters described recent findings that reveal the effects that diet may have on brain structure and function across the lifespan, as well as possible ways diet may be used to reverse the devastating effects of neurodegenerative disease.
Prenatal Diet Shapes Food Preference and Dopamine Signaling in Monkeys
The foundation for a person’s eating habits may be laid long before birth, according to studies demonstrating the association between maternal and childhood obesity. However, scientists have yet to identify how a mother’s body weight and food choices may have such an impact on her offspring. To examine how a mother’s high-fat diet affects her young, press conference presenter Heidi Rivera, a postdoctoral fellow in Elinor Sullivan’s laboratory at the Oregon National Primate Research Center, fed female monkeys either a high- or low-fat diet during gestation and lactation. After the offspring reached seven months (comparable in development to a human toddler), the researchers evaluated the food preferences of the offspring of the two groups.
Rivera found that despite receiving a low-fat diet, monkeys born to mothers on a high-fat diet showed a preference for food that was high in fat and sugar, compared with the offspring of mothers on a low-fat diet. When Rivera later examined the brains of the offspring at one year of age, she found the monkeys born to mothers that consumed a high-fat diet also had decreased dopamine projections to the prefrontal cortex.
“These findings suggest that eating a high-fat diet during pregnancy impairs the development of a brain circuit that regulates feeding behavior in monkey offspring,” Rivera said.
High-Fructose Diet Increases Depressive-Like Behaviors in Adolescent Rats
As the global number of people living with obesity continues to climb, so too does the number of people living with depression or other mental health conditions. Previous studies have found that, in addition to contributing to metabolic dysregulation, fructose consumption is associated with elevated production of stress hormones called glucocorticoids, which have been linked to anxiety and depression.
Because adolescents are the greatest consumers of fructose and adolescence marks a period of great brain development, press conference presenter Constance Harrell, a graduate student in Gretchen Neigh’s laboratory at Emory University, wondered whether high fructose consumption in adolescence could be changing the developing brain. She and her colleagues were particularly interested in whether such changes could be promoting long-term dysregulation of the stress response.
To address this question, Harrell and her colleagues fed young rats either a high-fructose or standard diet for 10 weeks. After 10 weeks, some of the animals were intermittently exposed to social defeat and restraint stress over a period of 12 days. Afterward, all animals underwent a series of tests to assess anxiety- and depressive-like behaviors. Compared with rats on a standard diet, animals fed a high-fructose diet displayed higher rates of anxiety-like behaviors in the elevated plus maze and higher rates of depressive-like behaviors in the forced swim test, irrespective of stress history. The fructose-fed rats also showed elevated baseline levels of the stress hormone corticosterone and changes in gene expression in the hypothalamus. These differences were not seen in rats fed fructose in adulthood only.
“A high-fructose diet [during adolescence] is at least potentially able to increase depressive- and anxiety-like behaviors, increase stress hormones, and cause widespread changes in gene expression in the brain,” Harrell said.
Obesity Leads to Greater Hippocampal Loss in Aging
Press conference presenters also discussed how diet affects the aging brain. While previous studies suggest obesity increases the risk of developing dementia, scientists continue to examine the biological basis of these changes. Press conference presenter Nicolas Cherbuin of the Australian National University described his work comparing hippocampal shrinkage in people who were overweight or obese to those of normal weight as they aged. The hippocampus, a region that is critical for memory formation, is implicated in Alzheimer’s disease and other dementias.
Cherbuin and colleagues scanned the brains and computed the body mass index of more than 400 60- to 64-year-olds multiple times over the course of eight years. As predicted, the hippocampal volume of the participants decreased over the course of the study. After controlling for age, gender, education, hypertension, depression, and other factors, the researchers found that participants who were obese or overweight had smaller hippocampi at the beginning of the study and greater hippocampal shrinkage over the eight-year period compared with people at a healthy weight.
“While we did not investigate the relationship between shrinkage and function, other studies in the field have shown that greater shrinkage in the hippocampus leads to a greater risk of cognitive decline and a greater risk of developing dementia,” Cherbuin said. Further studies are needed to explore the ways that obesity affects thinking abilities, he added.
‘Hunger Hormone’ Lessens Dopamine Cell Loss
Even as scientists continue to investigate how being overweight or obese affects cognitive abilities, efforts are ongoing to identify ways that diet can slow cell loss in aging. One potential intervention for diseases of aging is calorie restriction. Previous studies have found that reducing caloric intake may decrease dopaminergic cell loss in Parkinson’s disease and that the “hunger hormone” ghrelin may play a role in this protection. However, just how calorie restriction protects against neuronal loss remains unknown.
To better understand the relationship between a calorie-restricted diet, ghrelin, and the preservation of dopamine cells in Parkinson’s disease, press conference presenter Jacqueline Bayliss, a graduate student in the laboratory of Zane Andrews at Monash University in Melbourne, Australia, compared the effects of a calorie-restricted diet on Parkinson’s-model mice that could not produce ghrelin to Parkinson’s-model mice that could produce the hormone.
On a regular diet, Parkinson’s-model mice had fewer dopamine neurons in the substantia nigra pars compacta, the region of cell loss in Parkinson’s disease. While a calorie-restricted diet rescued some of the dopamine neurons in the Parkinson’s-model mice, this protective effect was not seen in the mice that could not produce ghrelin. When the researchers administered a single injection of ghrelin to normal mice, they found heightened dopamine levels in the substantia nigra and striatum.
“These findings suggest that ghrelin is responsible for the beneficial effects of calorie restriction in Parkinson’s disease,” Bayliss said.
A Healthy Diet for a Healthy Mind
At the conclusion of the press conference, DiLeone, who moderated the session, noted that while the studies presented at Neuroscience 2014 highlighted some of the perils of unhealthy diets in relation to brain development, mood disorders, and neurodegenerative diseases, they also demonstrated the power that a healthy diet can have on brain health. By continuing to explore the relationship between food and the brain, scientists hope to gain greater insight into the ways diet can promote brain wellness across the lifespan.