Expression of SV2 isoforms during rodent brain development.
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.
Laboratory of Developmental Neurobiology, GIGA-Neurosciences, University of Liege, Sart Tilman Liege B-4000, Belgium. Bernard.Rogister@ulg.ac.be.
Julie
J
Crèvecœur
Patrik
P
Foerch
Melissa
M
Doupagne
Caroline
C
Thielen
Catherine
C
Vandenplas
Gustave
G
Moonen
Manuel
M
Deprez
Bernard
B
Rogister
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000196:embryology* / Q000254:growth & development* / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D008562:Membrane Glycoproteins / Q000032:analysis / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D042282:Microdissection; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000096:biosynthesis*; D020033:Protein Isoforms / Q000032:analysis / Q000096:biosynthesis; D012640:Seizures / Q000378:metabolism*
D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; C489614:Sv2a protein, mouse