Brain Inflammation and Memory Loss
By OHIO STATE UNIVERSITY
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The study, building upon previous research from the same lab at The Ohio State
University, also showed that taking a DHA omega-3 fatty acid supplement for a month before the unhealthy
eating and surgical procedure prevented the effects on memory linked to both
the high-fat diet and the surgery in aged and young adult rats.
Inflammation and Memory Impairment
Three days on a high-fat diet alone was
detrimental to a specific type of fear-related memory in aged rats for as long
as two weeks later – the same type of impairment seen in younger rats that ate
fatty food and had a surgical procedure. The team has traced the brain
inflammation behind these effects to a protein that activates the immune
response.
“These data suggest that these multiple
insults have a compounding effect,” said senior author Ruth Barrientos, an
investigator in Ohio State’s Institute for Behavioral Medicine Research and
associate professor of psychiatry and behavioral health and neuroscience in the
College of Medicine.
“We’ve shown that an unhealthy diet, even in
the short term, especially when it’s consumed so close to a surgery, which in
and of itself will cause an inflammatory response, can have damaging results,”
Barrientos said. “The high-fat diet alone might increase inflammation in the
brain just a little bit, but then you have surgery that does the same thing,
and when put together in a short amount of time you get a synergistic response
that can set things in motion toward a longer-term memory issue.”
The study was published recently in the
journal Brain, Behavior, and Immunity.
Barrientos’ lab studies how everyday life
events might trigger inflammation in the aging brain as the nervous system
responds to signals from the immune system reacting to a threat. Decades of
research has suggested that with aging comes long-term “priming” of the brain’s
inflammatory profile and a loss of brain-cell reserve to bounce back.
Researchers fed young adult and aged rats a
diet high in saturated fat for three days before a procedure resembling
exploratory abdominal surgery – an event already known to cause about a week of
cognitive issues in an older brain. Control rats ate regular food and were
anesthetized, but had no surgery. (Barrientos’ lab has determined anesthesia
alone does not cause memory problems in rats.)
Research
Findings and Future Directions
In this study, as in previous research
on aged rats treated with morphine after surgery, the team
showed that an immune system receptor called TLR4 was the culprit behind the
brain inflammation and related memory problems generated by both surgery and
the high-fat diet, said first author Stephanie Muscat, assistant clinical
professor of neuroscience at Ohio State.
“Blocking the TLR4 signaling pathway prior to
the diet and surgery completely prevented that neuroimmune response and memory
impairments, which confirmed this specific mechanism,” Muscat said. “And as we
had found before in another model of an unhealthy diet, we showed that DHA
supplementation did mitigate those inflammatory effects and prevent memory
deficits after surgery.”
There were some surprising memory findings in
the new work. Different behavioral tasks are used to test two types of memory:
contextual memory based in the hippocampus and cued-fear memory based in the
amygdala. In contextual memory tests, rats with normal memory freeze when they
re-enter a room in which they had an unpleasant experience. Cued-fear memory is
evident when rats freeze in a new environment when they hear a sound connected
to that previous bad experience.
For aged rats in this study, as expected, the
combination of a high-fat diet and surgery led to problems with both contextual
and cued-fear memory that persisted for at least two weeks – a longer-lasting
effect than the researchers had seen before.
The high-fat diet alone also impaired the
aging rats’ cued-fear memory. And in young adult rats, the combination of the
high-fat diet and surgery led to only cued-fear memory deficits, but no
problems with memory governed by the hippocampus.
“What this is telling us in aged animals,
along with the fact we’re seeing this same impairment in young animals after
the high-fat diet and surgery, is that cued-fear memory is uniquely vulnerable
to the effects of diet. And we don’t know why,” Barrientos said. “One of the
things we’re hoping to understand in the future is the vulnerability of the
amygdala to these unhealthy diet challenges.”
With increasing evidence suggesting that
fatty and highly processed foods can trigger inflammation-related memory
problems in brains of all ages, the consistent findings that DHA – one of two
omega-3 fatty acids in fish and other seafood and available in supplement form
– has a protective effect are compelling, Barrientos said.
“DHA was really effective at preventing these
changes,” she said. “And that’s amazing – it really suggests that this could be
a potential pretreatment, especially if people know they’re going to have
surgery and their diet is unhealthy.”
Reference: “Post-operative cognitive
dysfunction is exacerbated by high-fat diet via TLR4 and prevented by dietary
DHA supplementation” by Stephanie M. Muscat, Michael J. Butler, Menaz N.
Bettes, James W. DeMarsh, Emmanuel A. Scaria, Nicholas P. Deems and Ruth M.
Barrientos, 23 December 2023, Brain,
Behavior, and Immunity.
DOI:
10.1016/j.bbi.2023.12.028
Co-authors included Michael Butler, Menaz
Bettes, James DeMarsh, Emmanuel Scaria and Nicholas Deems, all of Ohio State.
This work was supported by grants from the
National Institute on Aging and the National Institute of Neurological
Disorders and Stroke.
