title: Expression pattern of synaptic vesicle protein 2 (SV2) isoforms in patients with temporal lobe epilepsy and hippocampal sclerosis.
abstract: OBJECTIVE
  Synaptic vesicle proteins 2 (SV2) are neuronal vesicles membrane glycoproteins that appear as important targets in the treatment of partial and generalized epilepsies. Therefore, we analysed the expression of SV2 isoforms in the hippocampus of patients with temporal lobe epilepsy (TLE).
  
  
  METHODS
  SV2A, SV2B and SV2C immunostaining and QuantiGene branched DNA assay were performed on biopsies from 31 consecutive TLE patients with mesial temporal sclerosis (MTS) and compared with 10 autopsy controls. SV2 expression was further compared with Timm's staining, and synaptophysin, Zinc transporter 3 (ZnT3), dynorphin, vesicular glutamate transporter 1 (VGLUT1) and vesicular GABA transporter (VGAT) expression.
  
  
  RESULTS
  In TLE patients, SV2A and SV2B expression was decreased in areas of synaptic loss. SV2C, which is weakly expressed or absent in the hippocampus of controls, was overexpressed in 10/11 cases with classical MTS1A and mossy fibre sprouting but not in cases with other types of MTS. SV2C staining was located in the inner molecular layer of the dentate gyrus and colocalized with dynorphin, ZnT3 and VGLUT1, suggesting selective expression in presynaptic glutamatergic Zn(2+) -rich terminals of abnormal sprouting fibres. SV2 expression patterns correlated with histological subtypes of MTS, but not with clinical features or therapeutic regimens in this patient cohort.
  
  
  CONCLUSIONS
  In classical MTS1A, the expression of SV2 isoforms is altered with a marked decrease of SV2A and SV2B paralleling synaptic loss and a selective increase of SV2C in sprouting mossy fibres. These findings suggest a different physiology of sprouting synapses and the possibility to target them with SV2C-specific strategies.
authors.affiliation: Laboratory of Neuropathology, GIGA-Neurosciences, University of Liege, Liege, Belgium; Laboratory of Developmental Neurobiology, GIGA-Neurosciences, University of Liege, Liege, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Crèvecoeur
authors.forename: R M
authors.initials: RM
authors.lastname: Kaminski
authors.forename: B
authors.initials: B
authors.lastname: Rogister
authors.forename: P
authors.initials: P
authors.lastname: Foerch
authors.forename: C
authors.initials: C
authors.lastname: Vandenplas
authors.forename: M
authors.initials: M
authors.lastname: Neveux
authors.forename: M
authors.initials: M
authors.lastname: Mazzuferi
authors.forename: J
authors.initials: J
authors.lastname: Kroonen
authors.forename: C
authors.initials: C
authors.lastname: Poulet
authors.forename: D
authors.initials: D
authors.lastname: Martin
authors.forename: B
authors.initials: B
authors.lastname: Sadzot
authors.forename: E
authors.initials: E
authors.lastname: Rikir
authors.forename: H
authors.initials: H
authors.lastname: Klitgaard
authors.forename: G
authors.initials: G
authors.lastname: Moonen
authors.forename: M
authors.initials: M
authors.lastname: Deprez
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D012598:Sclerosis; D013569:Synapses / Q000378:metabolism; D055815:Young Adult
chemical_list: D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; C489616:SV2B protein, human; C585899:SV2C protein, human; C076414:SV2A protein, human
keywords: SV2; human; mesial temporal sclerosis; sprouting mossy fibres; temporal lobe epilepsy