Voeding rijk aan luteoline tegen geheugenverlies*
Uit een laboratorium en muizenonderzoek blijkt dat voeding rijk aan luteoline zoals selderie, peterselie en tijm goed is tegen
geheugenverlies bij het ouder worden. Het onderzoek richtten zich op de microglia, vrij kleine cellen van het centrale zenuwstelsel, die zorgen voor een afweersysteem van de hersenen. Bij infecties produceren deze microglia ontstekingsproteïnes (cytokines) die aanleiding kunnen zijn voor symptomen die een ziekte begeleiden zoals slapeloosheid, gebrek aan eetlust, geheugenproblemen en depressief gedrag. Bij het ouder worden produceren deze microglia ook meer en meer ontstekingscytokines. De bioactieve stof luteoline zorgde dat er flink minder cytokines geproduceerd werden. Oudere muizen met voeding rijk aan luteoline in de studie kregen door de extra luteoline in de voeding weer een werkgeheugen vergelijkbaar met
dat van de jongere muizen.
Age-Related Memory Deficits Reduced By Compound In Celery, Peppers
A diet rich in the plant 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.
Luteolin (LOOT-ee-oh-lin) is found in many plants, including carrots, peppers, celery, olive oil, peppermint, rosemary and
chamomile.
The new study, which examined the effects of dietary luteolin in a mouse model of aging, appears in the Journal of
Nutrition.
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.
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," he
said.
"We think this contributes to cognitive aging and is a predisposing factor for the development of neurodegenerative diseases."
Johnson has spent nearly a decade studying the anti-inflammatory properties of nutrients and various bioactive plant compounds, including luteolin. Previous studies - by Johnson's lab and others - have shown that luteolin has anti-inflammatory effects in the body. This is the first study to suggest, however, that luteolin improves cognitive health by acting directly on the microglial cells to reduce their production of inflammatory cytokines in the
brain.
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. 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.
Studies have shown that plant compounds such as luteolin can get into the brain, Johnson said. "We believe dietary luteolin accesses the brain and inhibits or reduces activation of microglial cells and the inflammatory cytokines they produce. This anti-inflammatory effect is likely the mechanism which allows their working memory to be restored to what it was at an earlier
age."
"These data suggest that consuming a healthy diet has the potential to reduce age-associated inflammation in the brain, which can result in better cognitive health," he
said.
The National Institutes of Health provided funding to support this research.
Abstract
A dysregulated overexpression of inflammatory mediators by microglia may facilitate cognitive aging and neurodegeneration. Considerable evidence suggests the flavonoid luteolin has antiinflammatory effects, but its ability to inhibit microglia, reduce inflammatory mediators, and improve hippocampal-dependent learning and memory in aged mice is unknown. In initial studies, pretreatment of BV-2 microglia with luteolin inhibited the induction of inflammatory genes and the release of inflammatory mediators after lipopolysaccharide (LPS) stimulation. Supernatants from LPS-stimulated microglia caused discernible death in Neuro.2a cells. However, treating microglia with luteolin prior to LPS reduced neuronal cell death caused by conditioned supernatants, indicating luteolin was neuroprotective. In subsequent studies, adult (3-6 mo) and aged (22-24 mo) mice were fed control or luteolin (20 mg/d)-supplemented diet for 4 wk and spatial working memory was assessed as were several inflammatory markers in the hippocampus. Aged mice fed control diet exhibited deficits in spatial working memory and expression of inflammatory markers in the hippocampus indicative of increased microglial cell activity. Luteolin consumption improved spatial working memory and restored expression of inflammatory markers in the hippocampus compared with that of young adults. Luteolin did not affect either spatial working memory or inflammatory markers in young adults. Taken together, the current findings suggest dietary luteolin enhanced spatial working memory by mitigating microglial-associated inflammation in the hippocampus. Therefore, luteolin consumption may be beneficial in preventing or treating conditions involving increased microglial cell activity and
inflammation. (Januari 2011)
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