High-fat diet in utero protects against Alzheimer's later
August 27, 2019
Science Daily/Temple University Health System
A high-fat diet can carry health risks, but for mothers-to-be, it may make all the difference when it comes to Alzheimer's disease prevention for their children. In a report published online August 26 in the journal Molecular Psychiatry, researchers at the Lewis Katz School of Medicine at Temple University show for the first time in animals that high maternal fat consumption during gestation protects offspring against changes in the brain that are characteristic of late-onset Alzheimer's disease.
"In humans, it has been known that individuals whose mothers develop Alzheimer's disease after age 65 are at increased risk of also developing the disease around the same age," said senior investigator Domenico Praticò, MD, Scott Richards North Star Foundation Chair for Alzheimer's Research, Professor in the Departments of Pharmacology and Microbiology, and Director of the Alzheimer's Center at Temple at the Lewis Katz School of Medicine.
Genetic factors transmitted by mothers to their offspring seem like an obvious explanation behind this phenomenon, but so far no genes have been identified that could explain the maternal transmission of Alzheimer's disease. This fact would suggest that environmental factors, such as lifestyle and diet, adopted during the gestation period, a time in which mother and baby are in tight interaction, could significantly influence the offspring's risk of developing the disease later in life.
Diet is of particular interest as a risk factor, especially a diet rich in animal fat and cholesterol. High-fat intake previously has been shown in young/adult mice to directly exacerbate the types of changes in brain function that ultimately may contribute to Alzheimer's disease.
To better understand the unique relationship between maternal Alzheimer's disease and risk in her offspring, Dr. Praticò and colleagues looked at maternal fat intake specifically during the gestation period in mice engineered to develop Alzheimer's disease. Pregnant mice were fed a high-fat diet from the beginning until the end of gestation. The moment offspring were born, mothers were switched to a regular diet, which was maintained during the lactation period. Offspring of these mothers were always kept at the same regular, or standard, diet throughout their life.
At 11 months of age, offspring underwent behavioral tests to assess learning ability and memory. "Surprisingly, we found that animals from mothers fed a high-fat diet during gestation had better learning and memory skills than their counterparts born to mothers fed a regular diet during gestation," Dr. Praticò said.
The observed improvements in memory and learning were associated with the maintenance of good synaptic integrity. In fact, offspring from mothers exposed to a high-fat diet had significant improvement of synapse function when compared with offspring from mothers on a regular diet. Synapses, the places where neurons come together to relay information, play a vital role in learning and memory formation.
In addition, compared to animals born to mothers fed a regular diet, offspring from mothers on a high-fat diet had lower levels of amyloid-beta, an abnormal protein that builds up in neurons, contributing to nerve cell dysfunction and eventually significant impairments in memory and learning
When the team searched for possible mechanisms responsible for the beneficial effect, they discovered that offspring from mothers fed a high-fat diet exhibited reduced levels of three important genes involved in Alzheimer's disease: beta-secretase, tau, and the pathological tau-regulating gene CDK5. Dr. Praticò's team found that already in the early developmental stages, the three genes were effectively switched off in offspring because the high-fat diet had increased activity of a protein called FOXP2. They demonstrated that the repressive activity of FOXP2 on these genes ultimately protected offspring from later declines in brain function and Alzheimer's disease development.
"Our findings suggest that, to be effective, Alzheimer's disease prevention probably needs to start very early in life, during gestation," Dr. Praticò said. "Diet at this specific life stage can have critical, but underestimated, long-term impacts on brain health."
Dr. Praticò and colleagues plan next to compare the effects of a high-fat diet to those of other diets, including diets high in sugar and protein and diets resembling the Mediterranean diet in humans. "We also want to see whether our findings can be replicated in wild-type animals" Dr. Praticò added.
https://www.sciencedaily.com/releases/2019/08/190827084717.htm
High-fat diet in pregnancy can cause mental health problems in offspring
Study is first to document causal relationship in study of nonhuman primates
July 21, 2017
Science Daily/Oregon Health & Science University
A high-fat diet during pregnancy alters the development of the brain and endocrine system of offspring, new research in an animal model suggests. The new study links an unhealthy diet during pregnancy to mental health disorders such as anxiety and depression in children.
"Given the high level of dietary fat consumption and maternal obesity in developed nations, these findings have important implications for the mental health of future generations," the researchers report.
The research was published in the journal Frontiers in Endocrinology.
The study, led by Elinor Sullivan, Ph.D., an assistant professor in the Division of Neuroscience at Oregon National Primate Research Center at OHSU, tested the effect of a maternal high-fat diet on nonhuman primates, tightly controlling their diet in a way that would be impossible in a human population. The study revealed behavioral changes in the offspring associated with impaired development of the central serotonin system in the brain. Further, it showed that introducing a healthy diet to the offspring at an early age failed to reverse the effect.
Previous observational studies in people correlated maternal obesity with a range of mental health and neurodevelopmental disorders in children. The new research demonstrates for the first time that a high-fat diet, increasingly common in the developed world, caused long-lasting mental health ramifications for the offspring of non-human primates.
In the United States, 64 percent of women of reproductive age are overweight and 35 percent are obese. The new study suggests that the U.S. obesity epidemic may be imposing transgenerational effects.
"It's not about blaming the mother," said Sullivan, senior author on the study. "It's about educating pregnant women about the potential risks of a high-fat diet in pregnancy and empowering them and their families to make healthy choices by providing support. We also need to craft public policies that promote healthy lifestyles and diets."
Researchers grouped a total of 65 female Japanese macaques into two groups, one given a high-fat diet and one a control diet during pregnancy. They subsequently measured and compared anxiety-like behavior among 135 offspring and found that both males and females exposed to a high-fat diet during pregnancy exhibited greater incidence of anxiety compared with those in the control group. The scientists also examined physiological differences between the two groups, finding that exposure to a high-fat diet during gestation and early in development impaired the development of neurons containing serotonin, a neurotransmitter that's critical in developing brains.
The new findings suggest that diet is at least as important as genetic predisposition to neurodevelopmental disorders such as anxiety or depression, said an OHSU pediatric psychiatrist who was not involved in the research.
"I think it's quite dramatic," said Joel Nigg, Ph.D., professor of psychiatry, pediatrics, and behavioral neuroscience in the OHSU School of Medicine. "A lot of people are going to be astonished to see that the maternal diet has this big of an effect on the behavior of the offspring. We've always looked at the link between obesity and physical diseases like heart disease, but this is really the clearest demonstration that it's also affecting the brain."
Sullivan and research assistant and first author Jacqueline Thompson said they believe the findings provide evidence that mobilizing public resources to provide healthy food and pre- and post-natal care to families of all socioeconomic classes could reduce mental health disorders in future generations.
"My hope is that increased public awareness about the origins of neuropsychiatric disorders can improve our identification and management of these conditions, both at an individual and societal level," Thompson said.
https://www.sciencedaily.com/releases/2017/07/170721164037.htm