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Theobromine Improves Working Memory by Activating the CaMKII/CREB/BDNF Pathway in Rats
Rafiad Islam1,2, Kentaro Matsuzaki3, Eri Sumiyoshi4
1Department of Environmental Physiology, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo 693-8501, Japan. rafiad@med.shimane-u.ac.jp.
Nutrients
|April 24, 2019
Summary
Theobromine (TB) from cacao beans may enhance working memory in rats by boosting the CaMKII/CREB/BDNF pathway in the brain. This study found increased levels of key proteins and improved cognitive function in rats supplemented with TB.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Theobromine (TB) is a methylxanthine in cacao beans.
- The Ca2+/calmodulin-dependent protein kinase II (CaMKII)/cAMP-response element-binding protein (CREB)/brain-derived neurotropic factor (BDNF) pathway is crucial for memory formation and gene expression.
- Understanding TB's effect on this pathway could reveal cognitive enhancement mechanisms.
Purpose of the Study:
- To investigate if theobromine (TB) supplementation improves cognitive and learning functions in rats.
- To determine if TB influences the CaMKII/CREB/BDNF signaling pathway in the medial prefrontal cortex (mPFC).
Main Methods:
- Male Wistar rats were fed a diet with or without 0.05% TB for 73 days.
- Cognitive abilities were assessed using the radial arm maze, novel object recognition, and Y-maze tests.
- Western blot, real-time PCR, and ELISA were used to measure p-CaMKII, p-CREB, and BDNF levels in the mPFC.
Main Results:
- Theobromine supplementation significantly improved working memory performance in rats across all behavioral tests.
- TB-fed rats exhibited significantly elevated levels of phosphorylated CaMKII (p-CaMKII) and phosphorylated CREB (p-CREB) in the mPFC.
- Both protein and mRNA levels of BDNF were significantly higher in the mPFC of TB-fed rats compared to controls.
Conclusions:
- Oral theobromine supplementation upregulates the CaMKII/CREB/BDNF pathway in the rat medial prefrontal cortex.
- This upregulation of the CaMKII/CREB/BDNF pathway by TB is associated with improved working memory in rats.
- Theobromine shows potential as a dietary supplement for cognitive enhancement.
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