Abstract
Recent epidemiological studies showed that daily coffee consumption is associated with a lower risk for several neurological disorders such as Alzheimer’s disease and Parkinson’s disease; however, the molecular mechanisms responsible for the protective effect of coffee against neurological disorders have not been elucidated. As brain-derived neurotrophic factor (BDNF) promotes neuronal survival and protects against neuronal damage, we investigated the effects of coffee on BDNF signaling using human neuroblastoma SH-SY5Y cells. We found that brewed coffee exerted an inhibitory effect on the autophosphorylation of tropomyosin receptor kinase B (TrkB), a BDNF receptor. Additionally, coffee reduced the phosphorylation of Akt in BDNF-treated SH-SY5Y cells. Treatment with coffee did not affect the TrkB receptor on the cell surface. The major constituents of coffee, such as caffeine, caffeic acid, chlorogenic acid, and trigonelline had no effect on TrkB phosphorylation induced by BDNF. In addition, coffee reduced the BDNF-induced increase in BDNF gene expression and the neurite outgrowth promoted by BDNF. Our data suggest that the protective effect of coffee reported in epidemiological studies against neurological disorders may not be associated with BDNF signaling through TrkB.
Highlights
Brain-derived neurotrophic factor (BDNF), a neurotrophin, is a member of the nerve growth factor (NGF)-re-How to cite this paper: Kakio, S., Nakazawa, Y., Funakoshi-Tago, M. and Tamura, H. (2015) Coffee Modulates the Function of Brain-Derived Neurotrophic Factor (BDNF) in Human Neuroblastoma SH-SY5Y Cells
To examine whether coffee affects the BDNF/tropomyosin receptor kinase B (TrkB) signaling pathway, we measured the effects of coffee on the autophosphorylation of TrkB elicited by BDNF binding in human neuroblastoma SH-SY5Y cells
Coffee reduced the phosphorylation of TrkB at tyrosine 516 (Y516), which is essential for Akt activation, in a concentration-dependent manner (Figure 2(A))
Summary
Brain-derived neurotrophic factor (BDNF), a neurotrophin, is a member of the nerve growth factor (NGF)-re-. A recent study proposed that caffeine might maintain the physiological levels of BDNF, as it had a positive effect on cognition [13]-[15] Another recent study showed that coffee fruit extract had a modulatory effect on the plasma levels of BDNF in healthy human subjects [16]. It is still unknown which molecular mechanism is responsible for the protective effect of coffee against neurological disorders associated with BDNF signaling. To investigate the possible role of BDNF in the protective effect of coffee against neurological disorders, we analyzed the effects of coffee on TrkB-mediated BDNF signaling in human neuroblastoma SH-SY5Y cells
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