| Autor: |
Pereira-Figueiredo D; Neurobiology of the Retina Laboratory, Fluminense Federal University, Niterói, RJ, Brazil.; Laboratory of Neurochemistry, Department of Neurobiology and Program of Neurosciences, Fluminense Federal University, Niterói, RJ, Brazil., Brito R; Cellular Signaling and Metabolic Modulation Laboratory, Cellular and Molecular Biology Department, Institute of Biology, Fluminense Federal University, Niterói, RJ, Brazil., Araújo DSM; Neurobiology of the Retina Laboratory, Fluminense Federal University, Niterói, RJ, Brazil.; Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy., Nascimento AA; Neurobiology of the Retina Laboratory, Fluminense Federal University, Niterói, RJ, Brazil.; Laboratory of Neurochemistry, Department of Neurobiology and Program of Neurosciences, Fluminense Federal University, Niterói, RJ, Brazil., Lyra ESB; Fundamental and Applied Analytical Chemistry Laboratory (LAQAFA), Department of Analytical Chemistry, Chemistry Institute, Fluminense Federal University, Niterói, RJ, Brazil., Cheibub AMSS; Fundamental and Applied Analytical Chemistry Laboratory (LAQAFA), Department of Analytical Chemistry, Chemistry Institute, Fluminense Federal University, Niterói, RJ, Brazil., Pereira Netto AD; Fundamental and Applied Analytical Chemistry Laboratory (LAQAFA), Department of Analytical Chemistry, Chemistry Institute, Fluminense Federal University, Niterói, RJ, Brazil., Ventura ALM; Laboratory of Neurochemistry, Department of Neurobiology and Program of Neurosciences, Fluminense Federal University, Niterói, RJ, Brazil.; Neurobiology Department, Biology Institute of Fluminense Federal University, Niteroi, Rio de Janeiro, Brazil., Paes-de-Carvalho R; Laboratory of Cellular Neurobiology, Fluminense Federal University, Niterói, RJ, Brazil.; Laboratory of Neurochemistry, Department of Neurobiology and Program of Neurosciences, Fluminense Federal University, Niterói, RJ, Brazil.; Neurobiology Department, Biology Institute of Fluminense Federal University, Niteroi, Rio de Janeiro, Brazil., Calaza KC; Neurobiology of the Retina Laboratory, Fluminense Federal University, Niterói, RJ, Brazil. kcalaza@id.uff.br.; Laboratory of Neurochemistry, Department of Neurobiology and Program of Neurosciences, Fluminense Federal University, Niterói, RJ, Brazil. kcalaza@id.uff.br.; Neurobiology Department, Biology Institute of Fluminense Federal University, Niteroi, Rio de Janeiro, Brazil. kcalaza@id.uff.br. |
| Abstrakt: |
In infants, the main cause of blindness is retinopathy of prematurity that stems in a hypoxic-ischemic condition. Caffeine is a psychoactive compound that at low to moderate concentrations, selectively inhibits adenosine A 1 and A 2A receptors. Caffeine exerts beneficial effects in central nervous system of adult animal models and humans, whereas it seems to have malefic effect on the developing tissue. We observed that 48-h exposure (during synaptogenesis) to a moderate dose of caffeine (30 mg/kg of egg) activated pro-survival signaling pathways, including ERK, CREB, and Akt phosphorylation, alongside BDNF production, and reduced retinal cell death promoted by oxygen glucose deprivation in the chick retina. Blockade of TrkB receptors and inhibition of CREB prevented caffeine protection effect. Similar signaling pathways were described in previously reported data concerning chemical preconditioning mechanism triggered by NMDA receptors activation, with low concentrations of agonist. In agreement to these data, caffeine increased NMDA receptor activity. Caffeine decreased the levels of the chloride co-transporter KCC2 and delayed the developmental shift on GABA A receptor response from depolarizing to hyperpolarizing. These results suggest that the caffeine-induced delaying in depolarizing effect of GABA could be facilitating NMDA receptor activity. DPCPX, an A 1 adenosine receptor antagonist, but not A 2A receptor inhibitor, mimicked the effect of caffeine, suggesting that the effect of caffeine occurs through A 1 receptor blockade. In summary, an in vivo caffeine exposure could increase the resistance of the retina to ischemia-induced cell death, by triggering survival pathways involving CREB phosphorylation and BDNF production/TrkB activation. |
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