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A recent study published in Neurobiology of Stress found that chronic early-life stress can lead to neuroinflammation and reduce the capacity of the hippocampus to create new neurons, resulting in cognitive deficits. However, supplementing the diet with 0.02% chlorogenic acid and 0.02% caffeic acid—both coffee polyphenols—can mitigate these adverse effects in mice.
Coffee polyphenols are bioactive compounds with antioxidant properties found in coffee, including chlorogenic acids, flavonoids, and lignans. These compounds help protect cells from oxidative stress and reduce inflammation, which can lower the risk of chronic diseases like cardiovascular disease and diabetes. Studies have also shown that coffee polyphenols can improve metabolic health by enhancing insulin sensitivity and reducing blood glucose levels. Additionally, they support cognitive function and may protect against neurodegenerative diseases such as Alzheimer’s disease.
Two key polyphenolic compounds in coffee are chlorogenic acid and caffeic acid. Chlorogenic acid is particularly abundant and has been linked to improved glucose metabolism and a reduced risk of chronic diseases. Caffeic acid, while less prevalent, also contributes to coffee’s health benefits by protecting cells from oxidative stress.
Study author Jorine Geertsema and her colleagues aimed to determine whether supplementing the diet of growing mice with chlorogenic and caffeic acid could protect against cognitive deficits induced by chronic early-life stress. Previous studies have shown that early stress can reduce the brain’s ability to produce new neurons (a process called hippocampal neurogenesis) and increase inflammation, leading to cognitive decline in adulthood. This study sought to explore the protective potential of coffee polyphenols against these adverse effects.
The study involved 47 male mice divided into four groups. Two groups were fed a standard grain-based diet, while the other two groups were given the same diet supplemented with 0.02% chlorogenic acid and 0.02% caffeic acid from the second to the forty-second day after birth. The mice were weaned at 21 days and continued on their respective diets until day 42, after which all groups were switched to a standard diet.
Within each pair of dietary groups, one group was exposed to early-life stress. This stress was induced by limiting the bedding material available to the mice and placing a steel grid mesh 1 cm above the bedding.
At four months of age, the mice underwent behavioral tests to assess their cognitive function. These tests included the object recognition task (ORT), the object location task (OLT), and the Morris water maze (MWM). After the behavioral tests, the researchers analyzed the mice’s brain tissue to determine the quantities of microglia cells (the brain’s immune cells) and the effectiveness of hippocampal neurogenesis.
The results showed that mice exposed to early-life stress gained less weight in the initial days of life. However, those that received the polyphenol-supplemented diet gained more weight during this period compared to those on the standard diet. By day 42, these weight differences had disappeared.
Behavioral tests conducted in adulthood confirmed that early-life stress led to cognitive deficits and a reduction in microglia cells in the hippocampus. However, this was only true for mice that were fed the standard diet. The mice on the polyphenol-supplemented diet did not exhibit these cognitive deficits or reductions in microglia cells.
The study authors believe that the coffee polyphenols protected the mice from cognitive deficits by supporting the survival of microglia cells in the brain. The protective effects could also be attributed to other mechanisms related to the antioxidant and anti-inflammatory properties of chlorogenic and caffeic acids.
“The supplementation of polyphenols in a diet emerges as a promising avenue for nutritional intervention in the context of mitigating the detrimental cognitive effects of ES [early stress] in males which are associated with microglial changes,” the study authors concluded.
The study sheds light on the effects of two coffee polyphenols on ameliorating cognitive decline caused by early-life stress. However, this study was done on mice and not on humans. Although mice share many physiological similarities with humans, they are different species, and the effects on humans may not be identical.
Future research should investigate whether these findings can be replicated in humans and explore the precise mechanisms through which coffee polyphenols exert their protective effects. Additionally, it would be valuable to study the potential benefits of these compounds in females and their effects when administered at different life stages.
The paper, “Coffee polyphenols ameliorate early-life stress-induced cognitive deficits in male mice,” was authored by J. Geertsema, M. Kratochvil, R. González-Domínguez, S. Lefèvre-Arbogast, D.Y. Low, A. Du Preez, H. Lee, M. Urpi-Sarda, A. Sánchez-Pla, L. Aigner, C. Samieri, C. Andres-Lacueva, C. Manach, S. Thuret, P.J. Lucassen, and A. Korosi.