In:
Neuropathology and Applied Neurobiology, Wiley, Vol. 40, No. 2 ( 2014-02), p. 191-204
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0305-1846
,
1365-2990
DOI:
10.1111/nan.2014.40.issue-2
Language:
English
Publisher:
Wiley
Publication Date:
2014
detail.hit.zdb_id:
2008293-9
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