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Expression pattern of synaptic vesicle protein 2 ( SV 2) isoforms in patients with temporal lobe epilepsy and hippocampal sclerosis
Author(s) -
Crèvecœur J.,
Kaminski R. M.,
Rogister B.,
Foerch P.,
Vandenplas C.,
Neveux M.,
Mazzuferi M.,
Kroonen J.,
Poulet C.,
Martin D.,
Sadzot B.,
Rikir E.,
Klitgaard H.,
Moonen G.,
Deprez M.
Publication year - 2014
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/nan.12054
Subject(s) - dentate gyrus , hippocampus , hippocampal sclerosis , synaptophysin , hippocampal formation , synaptic vesicle , biology , epilepsy , temporal lobe , pathology , glutamatergic , neuroscience , glutamate receptor , immunohistochemistry , medicine , vesicle , biochemistry , receptor , membrane
Aims Synaptic vesicle proteins 2 ( SV 2) are neuronal vesicles membrane glycoproteins that appear as important targets in the treatment of partial and generalized epilepsies. Therefore, we analysed the expression of SV 2 isoforms in the hippocampus of patients with temporal lobe epilepsy ( TLE ). Methods SV 2 A , SV 2 B and SV 2 C immunostaining and Q uanti G ene branched DNA assay were performed on biopsies from 31 consecutive TLE patients with mesial temporal sclerosis ( MTS ) and compared with 10 autopsy controls. SV 2 expression was further compared with T imm's staining, and synaptophysin, Z inc transporter 3 ( ZnT 3), dynorphin, vesicular glutamate transporter 1 ( VGLUT 1) and vesicular GABA transporter ( VGAT ) expression. Results In TLE patients, SV 2 A and SV 2 B expression was decreased in areas of synaptic loss. SV 2 C , which is weakly expressed or absent in the hippocampus of controls, was overexpressed in 10/11 cases with classical MTS 1 A and mossy fibre sprouting but not in cases with other types of MTS . SV 2 C staining was located in the inner molecular layer of the dentate gyrus and colocalized with dynorphin, ZnT 3 and VGLUT 1, suggesting selective expression in presynaptic glutamatergic Zn 2+ ‐rich terminals of abnormal sprouting fibres. SV 2 expression patterns correlated with histological subtypes of MTS , but not with clinical features or therapeutic regimens in this patient cohort. Conclusion In classical MTS 1 A , the expression of SV 2 isoforms is altered with a marked decrease of SV 2 A and SV 2 B paralleling synaptic loss and a selective increase of SV 2 C in sprouting mossy fibres. These findings suggest a different physiology of sprouting synapses and the possibility to target them with SV 2 C ‐specific strategies.