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- Title
Caffeine exposure alters adenosine system and neurochemical markers during retinal development.
- Authors
Brito, Rafael; Pereira‐Figueiredo, Danniel; Socodato, Renato; Paes‐de‐Carvalho, Roberto; Calaza, Karin C.
- Abstract
Evidence points to beneficial properties of caffeine in the adult central nervous system, but teratogenic effects have also been reported. Caffeine exerts most of its effects by antagonizing adenosine receptors, especially A1 and A2A subtypes. In this study, we evaluated the role of caffeine on the expression of components of the adenosinergic system in the developing avian retina and the impact of caffeine exposure upon specific markers for classical neurotransmitter systems. Caffeine exposure (5-30 mg/kg by in ovo injection) to 14-day-old chick embryos increased the expression of A1 receptors and concomitantly decreased A2A adenosine receptors expression after 48 h. Accordingly, caffeine (30 mg/kg) increased [3H]-8-cyclopentyl-1,3-dipropylxanthine (A1 antagonist) binding and reduced [3H]- ZM241385 (A2A antagonist) binding. The caffeine time-response curve demonstrated a reduction in A1 receptors 6 h after injection, but an increase after 18 and 24 h. In contrast, caffeine exposure increased the expression of A2A receptors from 18 and 24 h. Kinetic assays of [3H]-S-(4-nitrobenzyl)-6-thioinosine binding to the equilibrative adenosine transporter ENT1 revealed an increase in Bmax with no changes in Kd, an effect accompanied by an increase in adenosine uptake. Immunohistochemical analysis showed a decrease in retinal content of tyrosine hydroxylase, calbindin and choline acetyltransferase, but not Brn3a, after 48 h of caffeine injection. Furthermore, retinas exposed to caffeine had increased levels of phosphorylated extracellular signal-regulated kinase and cAMP-response element binding protein. Overall, we show an in vivo regulation of the adenosine system, extracellular signal-regulated kinase and cAMP-response element binding protein function and protein expression of specific neurotransmitter systems by caffeine in the developing retina.
- Subjects
CAFFEINE; ADENOSINES; RETINAL development; EYE development; BIOMARKERS
- Publication
Journal of Neurochemistry, 2016, Vol 138, Issue 4, p557
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/jnc.13683