Post-graduate theses
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| Identifier |
000377386 |
| Title |
Differential involvement of no and cGMP signaling pathway in the neuroprotective actions of somatostatin against AMPA induced excitoxicity in vivo |
| Alternative Title |
Η εμπλοκή του σηματοδοτικού μονοπατιού no cGMP στις νευροπροστατευτικές δράσεις της σωματοστατίνης έναντι στην επαγόμενη από το AMPA διεγερσικοτοξικότητα in vivo |
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Author
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Τσέλιου Μελπομένη
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Thesis advisor
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Θερμού, Κυριακή
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| Abstract |
The neuropeptide somatostatin and its selective analogs for the sst2 and sst5 receptor subtypes provided neuroprotection against AMPA induced retinal excitotoxicity in vivo (Kiagiadaki and Thermos, 2008; Kiagiadaki et al. 2010). The aim of the present study was to examine the mechanism mediating this protection with emphasize in the investigation of the possible involvement of the nitric oxide (NO)/ cGMP signaling pathway.
Adult female and male Sprague Dawley (250-300 g) rats were employed. The animals received intravitrealy PBS (50mM), AMPA (42nmol/eye), AMPA (42nmol) in combination with Lanreotide (sst2/5 selective ligand, 10-4M), AMPA (42nmol) in combination with L-817,818 (sst5 selective ligand, 10-4M), AMPA (42nmol) in combination with Lanreotide (10-4M) and L-NAME (nitric oxide synthase inhibitor,3, 30 nmol) or ODQ (soluble guanylate cyclase inhibitor, 10nmol) and AMPA (42nmol) in combination with L-817,818 (10-4M) and L-NAME (3, 30 nmol) or ODQ (10 nmol) or AMPA (42nmol) in combination with 8-Bromo-cGMP (membrane permeable cGMP analog, 1mM).
Immunohistochemistry studies using retinal markers against ChAT and bNOS, for cholinergic and neuronal NOS containing amacrine cells respectively, and caspase-3 immunoreactivity studies were employed to examine retinal cell loss and protection. Lanreotide and L-817,818 protected cholinergic and bNOS containing retinal cells from the AMPA insult. The inhibition of nitric oxide synthase (NOS) by L-NAME attenuated Lanreotide’s neuroprotective effect in a dose-dependent manner. The inhibition of soluble guanylate cyclase (sGC) activity by ODQ also reduced the neuroprotective actions of Lanreotide. These results suggest the involvement of NO/cGMP pathway in lanreotide’s neuroprotective actions. In addition, 8-Br-cGMP alone protected the retina from AMPA toxicity. In contrast with the Lanreotide’s inhibition by L-NAME, the L-817,818 neuroprotective actions did not reversed significantly by L-NAME. Whereas, the inhibition of sGC activity by ODQ attenuated the L-817,818 neuroprotective action, suggesting the involvement of a NO-independent sGC/cGMP signaling pathway in L-817,818 neuroprotective actions.
The above results indicate that a NO and/or sGC/cGMP mechanism is involved in the neuroprotective effects of the activation of somatostatin sst2 and sst5 receptor subtypes after AMPA induced excitotoxicity in retina and it would be in scientific interest the elucidation of the downstream pathways involved in this neuroprotection.
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| Language |
Greek |
| Subject |
Nervous system |
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Neuroprotection |
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Somatostatin |
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Somatostatin receptors |
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Νευροπροστασία |
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Σωματοστατίνη |
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Υποδοχές σωματοστατίνης |
| Issue date |
2012-12-11 |
| Collection
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School/Department--School of Medicine--Department of Medicine--Post-graduate theses
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Type of Work--Post-graduate theses
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| Permanent Link |
https://elocus.lib.uoc.gr//dlib/d/d/5/metadata-dlib-1355309838-388407-31573.tkl
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| Views |
184 |
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