Dietary Procyanidin C1 Improves Cognitive Function through MicroRNA-181a-5p

Area of Science:

• Neuroscience
• Molecular Biology
• Nutritional Science

Background:

• Procyanidin C1 (PC1), a polyphenol from cocoa, grapes, and apples, has known health benefits but low absorption and unknown mechanisms.
• Understanding how dietary compounds like PC1 affect neural function is crucial for developing effective health strategies.

Purpose of the Study:

• To elucidate the molecular mechanisms by which Procyanidin C1 (PC1) influences neural function and cognitive abilities.
• To identify key regulators involved in PC1's biological effects, particularly concerning brain health.

Main Methods:

• Investigated the effect of PC1 on spatial working memory and cognitive ability in vivo.
• Analyzed the role of circulating microRNA (miR)-181a-5p as a mediator of PC1's effects.
• Examined the involvement of the 67-kDa laminin receptor (67LR) in PC1-induced signaling.
• Assessed changes in brain-derived neurotrophic factor (BDNF), CREB, and ERK phosphorylation in the hippocampus.

Main Results:

• PC1 administration improved spatial working memory and cognitive ability.
• PC1 upregulated circulating miR-181a-5p via the 67LR pathway.
• Upregulation of miR-181a-5p by PC1 modulated BDNF and its downstream signaling.
• Inhibition of miR-181a-5p reversed PC1-induced cognitive improvements and molecular changes in the hippocampus.

Conclusions:

• PC1 enhances cognitive function through a mechanism involving the upregulation of miR-181a-5p via the 67LR.
• This pathway modulates BDNF signaling, impacting neural plasticity and cognitive regulation.
• The study reveals a novel gut-PC1-miRNA-67LR-BDNF axis influencing brain function, offering insights into poorly absorbed polyphenol efficacy.