Item


Role of the SV2A protein in epilepsy and Alzheimer’s mouse models

SV2s family proteins are neuronal vesicles membrane glycoproteins that are highly conserved in evolution (Janz & Südhof, 1999). It is known that SV2A isoform is the target to Levetiracetam (LEV), an effective anti-epileptic drug (B. Lynch et al., 2004). There are certain hypotheses about his role in epilepsy. However, his physiological function and its interaction with LEV remains unknown. Specifically, it is known that a specific type of Temporal Lobe Epilepsy (TLE) presents a reduction of SV2A expression associated with an upregulation of SV2C isoform (Crèvecoeur et al., 2014). The aims of this study consist in validating the proper operation of SV2A lox/lox sequence in order to invalidate SV2A expression and, secondly, analysing the expression of SV2B and SV2C in the absence of SV2A. For this purpose, a mouse line allowing the conditional removal of SV2A in the hippocampal region (CA3 and dentate gyrus (DG)) at postnatal stages 15 (P15) (Grik4:SV2A-cKO) was engineered. Unexpectedly, Grik4: SV2A-cKO transgenic mice did not present an epileptic phenotype. To determine the reason of these phenomenon, the concentration of the three isoforms was analysed and quantified. Results have shown a significant reduction of the quantity of SV2A transcript and protein in Grik4:SV2A-cKO animals hippocampus compared to the wild-type mice (WT). Together, these results confirmed the efficiency of the invalidation of SV2A in our mouse model. Parallel to these values, no significant change in SV2B or SV2C protein and transcript expression was observed implying an absence of compensation phenomenon. Nevertheless, many other hypotheses should be tested to explain this unexpected phenotype in Grik4: SV2AcKO mice. Finally, in order to resolve the role of SV2A in synaptic plasticity, a new nucleofection protocol for embryonic cortical neurons at the embryonic stage 16 (E16) in vitro was developed

Manager: Casadevall, Margarida
Rogister, Bernard
Other contributions: Universitat de Girona. Facultat de Ciències
Author: Sánchez Gil, Judit
Abstract: SV2s family proteins are neuronal vesicles membrane glycoproteins that are highly conserved in evolution (Janz & Südhof, 1999). It is known that SV2A isoform is the target to Levetiracetam (LEV), an effective anti-epileptic drug (B. Lynch et al., 2004). There are certain hypotheses about his role in epilepsy. However, his physiological function and its interaction with LEV remains unknown. Specifically, it is known that a specific type of Temporal Lobe Epilepsy (TLE) presents a reduction of SV2A expression associated with an upregulation of SV2C isoform (Crèvecoeur et al., 2014). The aims of this study consist in validating the proper operation of SV2A lox/lox sequence in order to invalidate SV2A expression and, secondly, analysing the expression of SV2B and SV2C in the absence of SV2A. For this purpose, a mouse line allowing the conditional removal of SV2A in the hippocampal region (CA3 and dentate gyrus (DG)) at postnatal stages 15 (P15) (Grik4:SV2A-cKO) was engineered. Unexpectedly, Grik4: SV2A-cKO transgenic mice did not present an epileptic phenotype. To determine the reason of these phenomenon, the concentration of the three isoforms was analysed and quantified. Results have shown a significant reduction of the quantity of SV2A transcript and protein in Grik4:SV2A-cKO animals hippocampus compared to the wild-type mice (WT). Together, these results confirmed the efficiency of the invalidation of SV2A in our mouse model. Parallel to these values, no significant change in SV2B or SV2C protein and transcript expression was observed implying an absence of compensation phenomenon. Nevertheless, many other hypotheses should be tested to explain this unexpected phenotype in Grik4: SV2AcKO mice. Finally, in order to resolve the role of SV2A in synaptic plasticity, a new nucleofection protocol for embryonic cortical neurons at the embryonic stage 16 (E16) in vitro was developed
Document access: http://hdl.handle.net/2072/298396
Language: eng
Rights: Attribution-NonCommercial-NoDerivs 3.0 Spain
Rights URI: http://creativecommons.org/licenses/by-nc-nd/3.0/es/
Subject: Transgenic mice
Epilepsy
Hippocampus (Brain)
Hipocamp
Epilèpsia
Ratolins transgènics
Title: Role of the SV2A protein in epilepsy and Alzheimer’s mouse models
Type: info:eu-repo/semantics/bachelorThesis
Repository: Recercat

Subjects

Authors