Vinciguerra, Antonio (2013) MicroRNA 103-1 EXERTS A NEUROPROTECTIVE EFFECT IN STROKE BY ENHANCING NCX1 EXPRESSION IN THE BRAIN. [Tesi di dottorato]

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Item Type: Tesi di dottorato
Lingua: English
Title: MicroRNA 103-1 EXERTS A NEUROPROTECTIVE EFFECT IN STROKE BY ENHANCING NCX1 EXPRESSION IN THE BRAIN
Creators:
CreatorsEmail
Vinciguerra, Antoniowinwar1985@yahoo.it
Date: 2 April 2013
Number of Pages: 101
Institution: Università degli Studi di Napoli Federico II
Department: Neuroscienze e Scienze Riproduttive ed Odontostomatologiche
Scuola di dottorato: Medicina molecolare
Dottorato: Neuroscienze
Ciclo di dottorato: 25
Coordinatore del Corso di dottorato:
nomeemail
Annunziato, Luciolannunzi@unina.it
Tutor:
nomeemail
Pignataro, Giuseppegpignata@unina.it
Date: 2 April 2013
Number of Pages: 101
Uncontrolled Keywords: microRNA, brain ischemia, sodium/cacium exchanger
Settori scientifico-disciplinari del MIUR: Area 05 - Scienze biologiche > BIO/14 - Farmacologia
Date Deposited: 10 Apr 2013 09:19
Last Modified: 18 Apr 2016 01:00
URI: http://www.fedoa.unina.it/id/eprint/9499

Abstract

Background and purpose: MicroRNAs (miRNA) are single-stranded short RNA molecules that regulate gene expression by either degradation or translational repression of mRNA. Recent studies showed that several neurodegenerative disorders including cerebral ischemia significantly alter cerebral miRNA profiles, mediating profound effect on the disease outcome. In that scenario the Na+/Ca2+ exchanger, by mediating Ca2+ and Na+ fluxes in a bidirectional way across the synaptic plasma membrane, may play a pivotal role in the events leading to anoxic damage. The objective of this study was to set up a valid therapeutical strategy able to contrast the role of specific miRNAs that downregulate NCX expression under experimental conditions mimicking stroke. Methods: NCX protein expression was evaluated after miRNA cell trasfection in PC12, BHK cell lines and neuronal cultures from rat embryons. Then, it has been tested the capability of AntimiRNA 103-1 to target mir-103-1 and to block its detrimental action on NCX1 RNA messanger. This second part has been conducted on a rat model of transient cerebral ischemia. Results: The results showed that NCX1 physiological expression was dramatically reduced when cells were treated with mir-103-1. This tight regulation of NCX by a specific microRNA represents the in vitro confirmation of a perfect complementarity existing between 3’UTR of NCX and seed sequence of miRNA 103-1 already evidenced by in silico analysis. Conversely, the in vivo approach consisted in administering, by intracerebroventricular infusion, miRNA 103-1 silencing (AntimiRNA) in a specific temporal delay from transient ischemia in which ischemic damage was at the highest level and NCX1 protein was strongly downregulated. Results showed that antimiRNA-103-1 protected brain from ischemia and sustained high level of neurobeneficial protein NCX1. Conclusions: The present findings support the idea that blocking mir-103-1 by microRNA inhibitor is a reasonable strategy to stop neurodetrimental downregulation of NCX occurring during ischemic conditions.

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