A study conducted in cell cultures at The Ohio State University shows that the omega-3 fatty acid DHA can reduce fat-induced inflammation at the cellular level, thereby protecting the brain from the harmful effects of an unhealthy diet. Another experiment using brain tissue from aging mice suggests that a high-fat diet may cause certain brain cells to overdo cell signaling, interfering with the creation of new memories.
In an earlier study of aging rats, the same lab found that a diet high in processed ingredients caused a strong inflammatory response in the brain and behavioral manifestations of memory loss, and that supplementing with DHA prevented these problems.
"The cool thing about this paper is that for the first time we can really start to differentiate these things by cell type," said senior author Ruth Barrientos, a researcher in the Institute for Behavioral Medicine at The Ohio State University and an associate professor of psychiatry and behavioral health and neuroscience in the College of Medicine. "Our lab and other labs often look at the overall organization of the hippocampus and look at the brain's memory response to a high-fat diet. But we've always been curious about which cell types are more or less affected by these saturated fatty acids, and this is the first time we've tried to determine that."
The research was recently published in the journal Frontiers in Cellular Neuroscience.
In this work, the researchers focused on microglia, cells in the brain that promote inflammation, and hippocampal neurons, which are important for learning and memory. They used immortalized cells - copies of cells taken from animal tissue that have been modified to divide continuously and respond only to laboratory stimuli, meaning they may not behave exactly like primary cells of the same type.
The researchers exposed these model microglia and neurons to palmitic acid, the most abundant saturated fatty acid found in high-fat foods such as lard, shortening, meat and dairy, to see how palmitic acid affected gene activation within the cells and the function of mitochondria, structures within cells that have the primary metabolic role of producing energy.
The results showed that palmitic acid prompted changes in gene expression that were associated with increased inflammation in microglia and neurons, but that a wider range of inflammatory genes were affected in microglia. Pretreating these cells with a dose of DHA, one of two omega-3 fatty acids found in fish and other seafood and also available in supplement form, had a strong protective effect against increased inflammation in both cell types.
"Previous studies have shown that DHA has a protective effect on the brain and that palmitic acid is harmful to brain cells, but this is the first time we have looked at how DHA directly protects against the effects of palmitic acid in these microglia," said Michael Butler, first author of the study and a research scientist in the Barrientos lab.
However, when it comes to mitochondria, DHA does not prevent the loss of function after exposure to palmitic acid. In this case, the protective effects of DHA may be limited to effects on gene expression related to pro-inflammatory responses, rather than the metabolic defects that saturated fat also induces.
In another set of experiments, the researchers examined how a diet high in saturated fat affected signaling in the brains of older mice by looking at another microglial function called synaptic pruning. Microglia monitor signaling between neurons and nibble away excess synaptic spines (the connection points between axons and dendrites) to maintain ideal levels of communication.
Microglia were exposed to mouse brain tissue containing pre- and postsynaptic material from animals fed a high-fat diet or regular chow for three days. Microglia ate the synapses of older mice on a high-fat diet at a faster rate than those of mice on a normal diet - suggesting that the high-fat diet had some effect on these synapses, giving microglia a reason to eat them at a higher rate.
"It's like 'Goldilocks' when we talk about the pruning or refinement that needs to be done: It needs to be in tip-top shape -- not too much, not too little," Butler said. "If these microglia eat too much too early, it overwhelms the ability of these spines to regrow and make new connections, so the memory can't be consolidated or stabilized."
From here, the researchers plan to expand on the findings related to synaptic pruning and mitochondrial function and look at the effects of palmitic acid and DHA in primary brain cells in young and old animals.