Expression of SV2 isoforms during rodent brain development

abstract: ...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.

... properly cited. 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. SV2 Mouse brain Development Epileptic seizures Background SV2 proteins are integral transmembrane proteins expressed on synaptic dense core vesicles [ 1 , 2 ] but are also found on small clear vesicles containing neurotransmitters [ 3 ]. Cloning of the individual family members resulted in the identification of three different isoforms, SV2A [ 1 ], SV2B [ 4 ] and SV2C [ 5 ]. The overall homology between the three rat isoforms is approximately 60%, with SV2A and SV2C being more similar to each other than SV2B [ 5 ]. SV2A is ubiquitously expressed in the central nervous system (CNS), neuroendocrine

... been identified yet, and the molecular function of SV2 proteins remains elusive. However, interactions with several synaptic proteins and hypothesis about their possible function have been reported. Botulinum Neurotoxin E was shown to interact with glycosilated forms of SV2A and SV2B [ 8 , 15 ]. Moreover, Mahrhold et al. reported that the carboxy-terminal region of SV2C intravesicular domain mediates the Botulinum Neurotoxin A entry leading to its toxic effects [ 16 ]. Several groups suggested a

... synaptic strength. SV2A, the major isoform in the CNS has been linked with seizures and an epileptic phenotype. SV2A KO animals are characterized by the onset of epileptic seizures in early postnatal stage (postnatal day 7 or P7) leading to death around P15 [ 17 , 27 ]. Moreover, it appears that SV2A expression decreases during epileptogenesis and chronically epileptic animals [ 28 - 30 ] as well as in patients with temporal lobe epilepsy [ 31 , 32 ]. The therapeutic interest of SV2 proteins has been

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Gene: SV2A - synaptic vesicle glycoprotein 2A - (NCBI)

Protein : 4v11

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