A plant compound found in carrots, peppers, celery, olive oil, peppermint, rosemary and chamomile helps reduce age-related inflammation in the brain and memory deficits, according to a new study conducted in mice.
The compound luteolin reduces age-related inflammation in the brain and related memory deficits by directly inhibiting the release of inflammatory molecules in the brain, researchers report.
The researchers focused on microglial cells, specialized immune cells that reside in the brain and spinal cord. Infections stimulate microglia to produce signaling molecules, called cytokines, which spur a cascade of chemical changes in the brain.
Some of these signaling molecules, the inflammatory cytokines, induce “sickness behavior”: the sleepiness, loss of appetite, memory deficits and depressive behaviors that often accompany illness.
Carrots
Inflammation in the brain also appears to be a key contributor to age-related memory problems, said University of Illinois animal sciences professor Rodney Johnson, who led the new study. Johnson directs the Division of Nutritional Sciences at Illinois.
“We found previously that during normal aging, microglial cells become dysregulated and begin producing excessive levels of inflammatory cytokines. We think this contributes to cognitive aging and is a predisposing factor for the development of neurodegenerative diseases,” he said.
Peppers
The researchers showed that microglial cells that were exposed to a bacterial toxin produced inflammatory cytokines that could kill neurons. When the microglia were exposed to luteolin before they encountered the toxin, however, the neurons lived.
“The neurons survived because the luteolin inhibited the production of neurotoxic inflammatory mediators,” Johnson said.
Exposing only the neurons to luteolin before the experiment had no effect on their survival, the researchers found.
“This demonstrated that luteolin isn”t protecting the neurons directly,” he said. “It”s doing it by affecting the microglial cells.”
The researchers next turned their attention to the effects of luteolin on the brains and behavior of adult (3- to 6-month-old) and aged (2-year-old) mice.
Celery
The mice were fed a control diet or a luteolin-supplemented diet for four weeks. The researchers assessed their spatial memory and measured levels of inflammatory markers in the hippocampus, a brain region that is important to memory and spatial awareness.
Normally, aged mice have higher levels of inflammatory molecules in the hippocampus and are more impaired on memory tests than younger adult mice.
Aged mice on the luteolin-supplemented diet, however, did better on the learning and memory task than their peers, and the levels of inflammatory cytokines in their brains were more like those of the younger adult mice.
“When we provided the old mice luteolin in the diet it reduced inflammation in the brain and at the same time restored working memory to what was seen in young cohorts,” Johnson said.
The new study appears in the Journal of Nutrition.
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The Daily Mail reported, “remembering to eat your celery could halt memory loss”. It said that a plant compound called luteolin found in celery and peppers “reduces inflammation in the brain, which is associated with ageing and its related memory problems”.
This news story reported on a small animal study, in which aged mice that were fed 20mg of luteolin a day performed better on a test of spatial memory. Using cells in the laboratory, the researchers also showed that luteolin could prevent the release of molecules that cause inflammation.
Although this is interesting basic research that may give insight into at least one of the processes involved as the brain ages, its direct relevance to humans is limited. The mice were given a relatively high supplement of pure luteolin. There is not sufficient evidence to suggest that normal dietary consumption of luteolin–rich vegetables such as celery can improve memory in humans.
Where did the story come from?
The study was carried out by researchers from the University of Illinois. It was funded by The National Institute of Health in the US. The study was published in the peer-reviewed Journal of Nutrition.
The Daily Mail’s report has exaggerated the relevance of this study to humans and the effect that eating celery might have on human memory.
What kind of research was this?
This laboratory study investigated how luteolin, an antioxidant found in celery, affected the inflammatory response of cells in tissue culture. The researchers then looked at how supplementing the diet of aged mice with luteolin affected their learning and memory.
What did the research involve?
This research was carried out in two parts. The first part investigated the effect of treating mouse cells with luteolin. The second part supplemented the diets of mice with luteolin and tested their spatial memory in a maze.
The cells in the first part were from a cell line called BV-2, which is a mouse microglial cell line. Microglia are a type of cell found in the brain, and they play a role in the brain’s inflammatory response to infection. The researchers made the cells have an inflammatory response by treating them with a chemical called lipopolysaccharide (LPS). Some of these microglial cells were also incubated with luteolin and their response to LPS then assessed.
The researchers also wanted to see whether inflammatory molecules released by the BV-2 cells in response to LPS would be toxic to neurones. To investigate this, they collected the liquid in which the BV-2 cells had been grown and placed this on a neurone cell line, then measured the amount of cell death.
In the second part of the study, the researchers compared the performance of older mice (two years old) and younger mice (three to six months old) in a maze, and examined whether a dietary supplement of luteolin affected this performance. The maze, a water maze, is designed to test spatial memory.
The researchers suggested that aged mice may have more brain inflammation and therefore worse memories, so should normally perform worse in the test. Here they wanted to test how luteolin might affect this. They used 26 adult mice and 26 aged mice. Half of each group was given a standard diet while the other half was also given a supplement of 20mg of luteolin a day for four weeks.
After the experiment, the researchers assessed how much luteolin had been absorbed into the mouse blood. They also looked at which genes had been switched on in the hippocampus, a region of the brain that is associated with spatial memory. They determined the activity of the genes by looking at how much RNA was produced by each gene.
What were the basic results?
When exposed to LPS alone, the inflammatory response in the BV-2 cells was characterised by a greater release of a peptide called interleukin -1? (IL-1?) and an increased activity in the gene that produces IL-1? and three other genes involved in inflammation that were measured.
BV-2 cells that had been treated with 50?mol/L of luteolin released 70% less IL-1? when exposed to LPS. Luteolin also reduced the activity of the gene that produced IL-1? and partially prevented the activity of the three other genes from being increased.
When the liquid (in which the BV-2 cells had been grown and treated with LPS) was mixed with neurone-like cells, some of the neurone-like cells died. However, BV-2 cells that had also been treated with luteolin caused a reduced amount of death of the neurone-like cells.
The researchers found that aged mice performed poorer on the water maze task, swimming further before they found the target. However, aged mice that had been given luteolin performed as well as the younger adult mice on this task. There was no difference in the performance of younger adult mice that had the luteolin-supplemented diet or normal diet.
The aged mice had higher levels of IL-1? mRNA in their hippocampus than adult mice, indicating that the IL-1? gene is more active in aged mice. The IL-I? gene was less active in the aged mice that had been fed luteolin.
How did the researchers interpret the results?
The researchers suggest that luteolin improves spatial working memory in aged mice by affecting the microglial-associated inflammation in the brain’s hippocampus. They suggest that luteolin consumption may be beneficial in preventing or treating conditions that involve increased microglial cell activity and inflammation.
Conclusion
This small animal study demonstrated that luteolin can interfere with microglial-mediated inflammation and improve spatial memory in aged mice, suggesting that microglial inflammation may play a role in spatial memory loss in mice.
This is a small animal study, and its relevance to human memory loss is limited. The mice were given 20mgs of luteolin per day, corresponding to 0.6% of their food intake. It is not clear if humans would need the same proportion to have a similar effect, whether this is feasible, or even if microglial–mediated inflammation plays a major role in memory impairment in normal ageing in humans.
This study provides further information into the basic science of ageing. Although it is common sense to eat vegetables such as celery and peppers as a source of fibre and vitamins, there is insufficient evidence to suggest that normal dietary consumption of luteolin–rich vegetables can improve memory.
A taste for celery is one that many people never acquire, but scientists have just given them a reason to eat it.
They have discovered that a chemical found in high concentrations in celery – and in peppers – could halt memory loss as we get older.
The U.S. researchers say the plant compound luteolin reduces inflammation in the brain, which is associated with ageing and its related memory problems, by halting the release of molecules that cause the inflammation.
The team from the University of Illinois studied the effects of luteolin on the brains and behaviour of young mice aged three to six months and older ones aged two years.