New research hints at a few ways fatty foods affect cells in the brain, a finding that could help explain the link between a high-fat diet and impaired memory – especially as we age.
The Ohio State University study in cell cultures found the omega-3 fatty acid DHA may help protect the brain from an unhealthy diet’s effects by curbing fat-induced inflammation at the cellular source.
Separate experiments using brain tissue from ageing mice showed a high-fat diet might lead specific brain cells to overdo cell-signalling management in a way that interferes with creating new memories.
The same lab found in an earlier study in ageing rats that a diet of highly processed ingredients led to a strong inflammatory response in the brain that was accompanied by behavioural signs of memory loss – and that DHA supplementation prevented those problems.
The cool thing about this paper is that for the first time, the researchers are really starting to tease these things apart by cell type, said senior author Ruth Barrientos, an investigator in Ohio State’s Institute for Behavioral Medicine Research and associate professor of psychiatry and behavioural health and neuroscience in the College of Medicine.
Labs have often investigated the whole hippocampus tissue to observe the brain’s memory-related response to a high-fat diet. Ruth Barrientos explained that this is the first step in determining which cell types are affected more or less by these saturated fatty acids.
The study was published recently in the journal Frontiers in Cellular Neuroscience.
Neurons in the hippocampus, which play a key role in learning and memory, and microglia, cells in the brain that cause inflammation were the focus of this study. They used immortalized cells – copies of cells taken from animal tissue modified to continuously divide and respond only to lab-based stimulation, meaning their behaviour may not precisely match that of primary cells of the same type.
These model microglia and neurons were subjected to palmitic acid, which is the most abundant saturated fatty acid found in high-fat foods like lard, shortening, meat, and dairy products. The researchers wanted to see how palmitic acid affected gene activation in the cells as well as the functioning of mitochondria, which are structures within cells that have a primary metabolic role of generating energy.
Previous work has shown that DHA is protective in the brain and that palmitic acid has been detrimental to brain cells, but this is the first time the researchers have looked at how DHA can directly protect against the effects of palmitic acid in those microglia and the research sees that there is a strong protective effect, said Michael Butler, first author of the study and a research scientist in Barrientos’ lab.
When it came to the mitochondria, however, DHA did not prevent the loss of function that followed exposure to palmitic acid.
In this context, the protective effects of DHA might be restricted to effects on gene expression related to the pro-inflammatory response as opposed to the metabolic deficits that the saturated fat also induced, Butler said.
In another set of experiments, the researchers looked at how a diet high in saturated fat influenced signalling in the brains of aged mice by observing another microglial function called synaptic pruning. Microglia monitor signal transmission among neurons and nibble away excess synaptic spines, the connection sites between axons and dendrites, to keep communication at an ideal level.
Microglia were exposed to mouse brain tissue containing both pre-and post-synaptic material from animals that had been fed either a high-fat diet or regular chow for three days.
The microglia ate the synapses from aged mice fed a high-fat diet at a faster rate than they ate synapses from mice fed a regular diet – suggesting the high-fat diet is doing something to those synapses that give the microglia a reason to eat them at a higher rate, Butler said.
Pruning, or refinement that needs to occur, is like Goldilocks and needs to be optimal – not too much or too little, Barrientos said. With these microglia eating away too much too soon, it outpaces the ability of these spines to regrow and create new connections, so memories don’t solidify or become stable, he adds.
From here, the researchers plan to expand on synaptic pruning and mitochondria function findings and see how palmitic acid and DHA effects play out in primary brain cells from young versus aged animals.
Grants from the National Institute on Aging and the National Institute of Dental and Craniofacial Research supported this work. Additional co-authors, all from Ohio State, were Sabrina Mackey-Alfonso, Nashali Massa and Kedryn Baskin.
