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Identifier 000403386
Title Investigation of the cannabinoid system in healthy and ischemic retina
Alternative Title Μελέτη της επίδρασης του κανναβινοειδικού συστήματος στον υγιή και ισχαιμικό αμφιβληστροειδή
Author Παπαδογκωνάκη, Σοφία
Thesis advisor Θερμού, Κυριακή
Reviewer Λιαπάκης, Γεώργιος
Χαραλαμπόπουλος, Ιωάννης
Abstract Cannabinoids have been shown to protect the retina, in different models of neurotoxicity via activation of the CB1 receptor (CB1R) and its downstream PI3K/Akt signaling pathway. Chronic exposure of the synthetic cannabinoid HU-210 induced the downregulation of the CB1R in several brain regions. The aim of this study was to investigate whether subchronic or chronic administration of HU-210 leads to downregulation of the CB1R in healthy and ischemic rat retina. Sprague-Dawley rats were administered with HU-210 (25, 50 and 100 μg/kg, i.p) daily for 4 or 14 days (subchronic or chronic administration). To study the acute effects of HU-210, rats were injected with vehicle for 13 days and with HU-210 on the 14th day. Immunohistochemical studies and western blot analysis were performed to examine the downregulation of the CB1R and the phosphorylation of Akt protein. Acute and subchronic effects of HU-210 on CB1 receptor expression and on the neuroprotection of amacrine cells in the in vivo model of AMPA excitotoxicity were examined. CB1R immunoreactivity is localized in the ganglion cell, inner plexiform, inner nuclear and outer plexiform layers. A decrease of CB1R immunoreactivity was observed after 4 or 14 days of HU-210 (50 and 100 μg/kg, i.p.) administration. Similar results were obtained with western blot analysis. Acute administration of HU-210 (100μg/kg) decreased the CB1R immunoreactivity. This dose also led to the reduction of Akt phosphorylation after chronic treatment. Co-administration of HU-210 (10-6 M) with AMPA (8.4mM) afforded neuroprotection to retinal amacrine cells against AMPA excitotoxicity, while subchronic administration of HU-210 (50μg/kg, i.p) attenuated this effect and decreased CB1R immunoreactivity. This study provides novel information regarding the chronic effect of HU-210 in healthy rat retinas and in animal models of retinopathy. HU-210, caused a time- and dose-dependent downregulation of the CB1R in rat retina and a reduction in the activation of PI3K/Akt signalling pathway. Down regulation of the CB1R was also observed after subchronic administration of HU-210, in the AMPA excitotoxicity model, leading to the loss of neuroprotection to amacrine cells. These results suggest that HU-210 does not appear to be the appropriate therapeutic for chronic retinopathies.
Language English
Subject Neuroprotection
Tachyphylaxis
Αμφιβληστροειδοπάθειες
Νευροπροστασία
Νευροπροστασία
Ταχυφυλαξία
Issue date 2016-12-13
Collection   School/Department--School of Medicine--Department of Medicine--Post-graduate theses
  Type of Work--Post-graduate theses
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