Your browser does not support JavaScript!

Home    Μελέτη της επίδρασης της υποχρόνιας ενδοπεριτοναϊκής χορήγησης του κανναβινοειδούς R-WIN55,212-2 στην έκφραση του CB1 υποδοχέα στον φυσιολογικό αμφιβληστροειδή και στο μοντέλο της επαγόμενης από το AMPA διεγερτοτοξικότητας  

Results - Details

Add to Basket
[Add to Basket]
Identifier 000419920
Title Μελέτη της επίδρασης της υποχρόνιας ενδοπεριτοναϊκής χορήγησης του κανναβινοειδούς R-WIN55,212-2 στην έκφραση του CB1 υποδοχέα στον φυσιολογικό αμφιβληστροειδή και στο μοντέλο της επαγόμενης από το AMPA διεγερτοτοξικότητας
Alternative Title Effect of sub chronic intraperitoneal administration of the synthetic CB1/CB2 cannabinoid, WIN 55 212-2, on the expression of the CB1 receptor in healthy retinal and in the model of AMPA excitotoxicity"
Author Σπυριδάκος, Δημήτριος
Thesis advisor Θερμού, Κυριακή
Reviewer Καστελλάκης, Ανδρέας
Χαραλαμπόπουλος, Ιωάννης
Abstract Cannabinoids have been shown to exert neuroprotective effects in many models of neurotoxicity in the retina, including AMPA induced excitotoxicity. These effects are mediated mainly through the CB1 receptor, located in many different cell populations in the retina. However studies in the brain and retina have shown, that chronic or subchronic use of cannabinoid agonists causes downregulation of CB1 receptors, something that interferes with their neuroprotective actions. The goal of the present study is to investigate the neuroprotective action of the synthetic cannabinoid CB1/CB2 agonist, WIN55,212-2, in the AMPA model of excitotoxicity in rat retina and also to examine its effects, after subcronic administration, in the expression of CB1 receptor. Sprague-Dawley rats received intravitreal injections of PBS or AMPA, in the absence or presence of WIN55,212-2 (10-6, 10-5 & 10-4 M). In the subchronic model, WIN55,212-2 was administered intraperitoneally (i.p), for 4 days in healthy rats or in rats, that were administered AMPA intravitreally. Immunohistochemical studies were performed, in order to assess the viability of retinal cells and to examine CB1 expression in healthy and AMPA treated retinas. Intravitreal administration of WIN55,212-2 protected bNOS expressing amacrine cells, an effect that was blocked by co-administration of the CB1 antagonist/inverse agonist, AM251. Also WIN55,212-2 reduced the activation of microglia. Subchronic administration of WIN55,212-2 protected bNOS expressing amacrine cells at the dose of 25 μg/kg, but there was no such effect at the dose of 100 μg/kg. The latter may be due to the fact that the dose of 100 μg/kg, WIN55,212-2 induced the downregulation of the CB1 receptor in both healthy and AMPA treated retinas. No such downregulation was observed at doses of 25 and 50 μg/kg . Collectively these data suggest that WIN55,212-2 exerts neuroprotective actions in the AMPA excitotoxicity model when administered acutely. Subchronic administration of high doses of WIN55,212-2 leads to the downregulation of the CB1 receptor and reduces its neuroprotective actions.
Language Greek, English
Subject Intravitreal injection
Subchronic administration
Βραχύινα κύτταρα
Ενδοφθάλμια έγχυση
Νευροπροστασία
Issue date 2018-12-05
Collection   School/Department--School of Medicine--Department of Medicine--Post-graduate theses
  Type of Work--Post-graduate theses
Views 251

Digital Documents
No preview available

Download document
View document
Views : 16