Abstract
Purpose: Some reports have shown neuroprotective effects of
caffeine in several neurodegenerative disorders. However, its mechanism of
action is not completely clear. Therefore, the aim of
this study was to explore the interference of ryanodine, N-methyl-D-aspartate
(NMDA) and adenosine modulators with the neuroprotective effects of caffeine
against β-amyloid (Aβ) neurotoxicity in the
SHSY5Y cells.
Methods: The
SHSY5Y cells were treated with Aβ23-35 (20µM)
and/or caffeine (0.6 and 1mM), or both for 24 hours. Adenosine (20, 40, 60, 80,
100µM), NMDA (20, 50, 70, 90µM), dantrolene (2, 4, 6, 8, 10µM) were also added
to the medium and incubated for 24 hours. The cell viability was measured via
the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) method.
The data were analyzed using one-way ANOVA followed by Bonferroni test.
Results: Caffeine at all the used concentrations (0.6, 0.8,
0.9, 1, and 3mM) significantly protected neuronal cells against Aβ
neurotoxicity. Adenosine at the concentrations of 20, 40, 80 and 100μM
diminished the neuroprotective effects of caffeine (0.6 and 1mM) against Aβ
neurotoxicity. NMDA at the concentrations of 20, 50, 70 and 90μM blocked
caffeine (0.6 and 1mM) neuroprotective effects. Dantrolene at the concentration
of 2, 4, 6, 8 and 10μM diminished the neuroprotective effects of caffeine
(0.6mM) and at the concentrations of 2 and 10μM impede caffeine (1mM)
neuroprotection against Aβ neurotoxicity.
Conclusion: Caffeine produced neuroprotective effect against
Aβ neurotoxicity. Blockade of adenosine and NMDA receptors, as well as the
activation of ryanodine receptors, may contribute to the neuroprotective
effects of caffeine.