Expression of SV2 isoforms during rodent brain development

BMC Neuroscience

Bernard Rogister²  Manuel Deprez⁴  Gustave Moonen¹  Catherine Vandenplas⁵  Caroline Thielen³  Melissa Doupagne³  Patrik Foerch⁵  Julie Crèvecœur⁴ 

[1] Departement of Neurology, CHU, University of Liege, Sart Tilman, Liege B-4000, Belgium;Laboratory of Developmental Neurobiology, GIGA-Development, Stem Cells and Regenerative Medicine, University of Liege, Sart Tilman, Liege B-4000, Belgium;Laboratory of Developmental Neurobiology, GIGA-Neurosciences, University of Liege, Sart Tilman Liege B-4000, Belgium;Laboratory of Neuropathology, GIGA-Neurosciences, University of Liege, Sart Tilman, Liege B-4000, Belgium;UCB Pharma S.A., CNS Research, Braine-l’Alleud B-1420, Belgium

关键词: Epileptic seizures;    Development;    Mouse brain;    SV2;   

Others  :  1140149
DOI  :  10.1186/1471-2202-14-87

 received in 2012-06-26, accepted in 2013-08-05,  发布年份 2013

【 摘 要 】

Background

SV2A, SV2B and SV2C are synaptic vesicle proteins that are structurally related to members of the major facilitator superfamily (MFS). The function and transported substrate of the SV2 proteins is not clearly defined although they are linked to neurotransmitters release in a presynaptic calcium concentration-dependent manner. SV2A and SV2B exhibit broad expression in the central nervous system while SV2C appears to be more restricted in defined areas such as striatum. SV2A knockout mice start to display generalized seizures at a late developmental stage, around post-natal day 7 (P7), and die around P15. More recently, SV2A was demonstrated to be the molecular target of levetiracetam, an approved anti-epileptic drug (AED). The purpose of this work was to precisely analyze and quantify the SV2A, SV2B and SV2C expression during brain development to understand the contribution of these proteins in brain development and their impact on epileptic seizures.

Results

First, we systematically analyzed by immunohistofluorescence, the SV2A, SV2B and SV2C expression during mouse brain development, from embryonic day 12 (E12) to P30. This semi-quantitative approach suggests a modulation of SV2A and SV2B expression in hippocampus around P7. This is the reason why we used various quantitative approaches (laser microdissection of whole hippocampus followed by qRT-PCR and western blot analysis) indicating that SV2A and SV2B expression increased between P5 and P7 and remained stable between P7 and P10. Moreover, the increase of SV2A expression in the hippocampus at P7 was mainly observed in the CA1 region while SV2B expression in this region remains stable.

Conclusions

The observed alterations of SV2A expression in hippocampus are consistent with the appearance of seizures in SV2A−/− animals at early postnatal age and the hypothesis that SV2A absence favors epileptic seizures around P7.

【 授权许可】

   
2013 Crèvecœur et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

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