Expression pattern of synaptic vesicle protein 2 ( SV2) isoforms in patients with temporal lobe epilepsy and hippocampal sclerosis.

Autor: 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.
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Zdroj: Neuropathology & Applied Neurobiology; Apr2014, Vol. 40 Issue 2, p191-204, 14p
Abstrakt: Aims 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 SV2 A, SV2 B and SV2 C immunostaining and Quanti Gene 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, SV2 A and SV2 B expression was decreased in areas of synaptic loss. SV2 C, which is weakly expressed or absent in the hippocampus of controls, was overexpressed in 10/11 cases with classical MTS1 A and mossy fibre sprouting but not in cases with other types of MTS. SV2 C 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 Zn2+-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. Conclusion In classical MTS1 A, the expression of SV2 isoforms is altered with a marked decrease of SV2 A and SV2 B paralleling synaptic loss and a selective increase of SV2 C in sprouting mossy fibres. These findings suggest a different physiology of sprouting synapses and the possibility to target them with SV2 C-specific strategies. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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