How Saturated Fats May Hinder Memory Formation in the Aging Brain

A brand new examine suggests {that a} high-fat eating regimen might impair reminiscence by inflicting inflammatory results and points in cell-signaling administration in the mind cells, particularly as folks age, however the omega-3 fatty acid DHA might assist mitigate these results. The analysis, specializing in microglia and hippocampal neurons, discovered that palmitic acid elevated irritation, whereas DHA protected in opposition to this impact however not in opposition to the loss of mitochondrial operate induced by palmitic acid publicity.

New analysis reveals DHA shields mind cells from fat-related irritation.

New analysis suggests a number of mechanisms by way of which high-fat meals might impression mind cells, doubtlessly elucidating the affiliation between a high-fat eating regimen and reminiscence decline, significantly in getting older.

A examine from The Ohio State University carried out in cell cultures signifies that the omega-3 fatty acid DHA may defend the mind from the detrimental results of an unhealthy eating regimen by decreasing fat-triggered irritation at the mobile degree.

Separate experiments utilizing mind tissue from getting older mice confirmed a high-fat eating regimen might lead particular mind cells to overdo cell-signaling administration in a means that interferes with the creation of recent recollections.

The identical lab discovered in an earlier examine in getting older rats {that a} eating regimen of extremely processed elements led to a powerful inflammatory response in the mind that was accompanied by behavioral indicators of reminiscence loss – and that DHA supplementation prevented these issues.

“The cool thing about this paper is that for the first time, we’re really starting to tease these things apart by cell type,” stated senior writer Ruth Barrientos, an investigator in Ohio State’s Institute for Behavioral Medicine Research and affiliate professor of psychiatry and behavioral health and neuroscience in the College of Medicine.

“Our lab and others have often looked at the whole tissue of the hippocampus to observe the brain’s memory-related response to a high-fat diet. But we’ve been curious about which cell types are more or less affected by these saturated fatty acids, and this is our first foray into determining that.”

The examine was revealed lately in the journal Frontiers in Cellular Neuroscience.

For this work, the researchers targeted on microglia, cells in the mind that promote irritation, and hippocampal neurons, that are necessary for studying and reminiscence. They used immortalized cells – copies of cells taken from animal tissue which can be modified to repeatedly divide and reply solely to lab-based stimulation, that means their habits might not exactly match that of main cells of the identical sort.

Researchers uncovered these mannequin microglia and neurons to palmitic acid, the most considerable saturated fatty acid in high-fat meals like lard, shortening, meat, and dairy merchandise, to watch the way it affected gene activation in the cells in addition to functioning of mitochondria, constructions inside cells which have a main metabolic function of producing vitality.

Results confirmed that palmitic acid prompted gene expression adjustments linked to a rise in irritation in each microglia and neurons, although microglia had a wider vary of affected inflammatory genes. Pre-treatment of those cells with a dose of DHA, one in all two omega-3 fatty acids in fish and different seafood and obtainable in complement kind, had a powerful protecting impact in opposition to the elevated irritation in each cell sorts.

“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 we’ve looked at how DHA can directly protect against the effects of palmitic acid in those microglia, and we see that there is a strong protective effect,” stated Michael Butler, first writer of the examine and a analysis scientist in Barrientos’ lab.

When it got here to the mitochondria, nonetheless, DHA didn’t forestall the loss of operate that adopted publicity to palmitic acid.

“The protective effects of DHA might, in this context, 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 stated.

In one other set of experiments, the researchers checked out how a eating regimen high in saturated fats influenced signaling in the brains of aged mice by observing one other microglial operate referred to as synaptic pruning. Microglia monitor sign transmission amongst neurons and nibble away extra synaptic spines, the connection websites between axons and dendrites, to maintain communication at a perfect degree.

Microglia have been uncovered to mouse mind tissue containing each pre- and post-synaptic materials from animals that had been fed both a high-fat eating regimen or common chow for 3 days.

The microglia ate the synapses from aged mice fed a high-fat eating regimen at a quicker fee than they ate synapses from mice fed an everyday eating regimen – suggesting the high-fat eating regimen is doing one thing to these synapses that provides the microglia a purpose to eat them at the next fee, Butler stated.

“When we talk about the pruning, or refinement, that needs to occur, it’s like Goldilocks: It needs to be optimal – not too much and not too little,” Barrientos stated. “With these microglia eating away too much too soon, it outpaces the ability for these spines to regrow and create new connections, so memories don’t solidify or become stable.”

From right here, the researchers plan to increase on findings associated to synaptic pruning and mitochondria operate, and to see how palmitic acid and DHA results play out in main mind cells from younger versus aged animals.

Reference: “Dietary fatty acids differentially impact phagocytosis, inflammatory gene expression, and mitochondrial respiration in microglial and neuronal cell models” by Michael J. Butler, Sabrina E. Mackey-Alfonso, Nashali Massa, Kedryn Okay. Baskin and Ruth M. Barrientos, 10 August 2023, Frontiers in Cellular Neuroscience.
DOI: 10.3389/fncel.2023.1227241

This work was supported by grants from the National Institute on Aging and the National Institute of Dental and Craniofacial Research. Additional co-authors, all from Ohio State, have been Sabrina Mackey-Alfonso, Nashali Massa and Kedryn Baskin.

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