-
- D Boido, P Farisello, F Cesca, E Ferrea, F Valtorta, F Benfenati, and P Baldelli.
- Department of Neuroscience and Brain Technologies, The Italian Institute of Technology, Via Morego 30, 16163 Genova, Italy.
- Neuroscience. 2010 Nov 24; 171 (1): 268-83.
AbstractSynapsins (SynI, SynII, SynIII) are a multigene family of synaptic vesicle (SV) phosphoproteins implicated in the regulation of synaptic transmission and plasticity. Synapsin I, II, I/II and I/II/III knockout mice are epileptic and SYN1/2 genes have been identified as major epilepsy susceptibility genes in humans. We analyzed cortico-hippocampal epileptiform activity induced by 4-aminopyridine (4AP) in acute slices from presymptomatic (3-weeks-old) and symptomatic (1-year-old) Syn I/II/III triple knockout (TKO) mice and aged-matched triple wild type (TWT) controls and assessed the effect of the SV-targeted antiepileptic drug (AED) levetiracetam (LEV) in reverting the epileptic phenotype. Both fast and slow interictal (I-IC) and ictal (IC) events were observed in both genotypes. The incidence of fast I-IC events was higher in presymptomatic TKO slices, while frequency and latency of I-IC events were similar in both genotypes. The major age and genotype effects were observed in IC activity, that was much more pronounced in 3-weeks-old TKO and persisted with age, while it disappeared from 1-year-old TWT slices. LEV virtually suppressed fast I-IC and IC discharges from 3-weeks-old TWT slices, while it only increased the latency of fast I-IC and IC activity in TKO slices. Analysis of I-IC events in patch-clamped CA1 pyramidal neurons revealed that LEV increased the inhibitory/excitatory ratio of I-IC activity in both genotypes. The lower LEV potency in TKO slices of both ages was associated with a decreased expression of SV2A, a SV protein acting as LEV receptor, in cortex and hippocampus. The results demonstrate that deletion of Syn genes is associated with a higher propensity to 4AP-induced epileptic paroxysms that precedes the onset of epilepsy and consolidates with age. LEV ameliorates such hyper excitability by enhancing the inhibition/excitation ratio, although the effect is hindered in TKO slices which exhibit a concomitant decrease in the levels of the LEV receptor SV2A.Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.
Notes
Knowledge, pearl, summary or comment to share?You can also include formatting, links, images and footnotes in your notes
- Simple formatting can be added to notes, such as
*italics*
,_underline_
or**bold**
. - Superscript can be denoted by
<sup>text</sup>
and subscript<sub>text</sub>
. - Numbered or bulleted lists can be created using either numbered lines
1. 2. 3.
, hyphens-
or asterisks*
. - Links can be included with:
[my link to pubmed](http://pubmed.com)
- Images can be included with:
![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
- For footnotes use
[^1](This is a footnote.)
inline. - Or use an inline reference
[^1]
to refer to a longer footnote elseweher in the document[^1]: This is a long footnote.
.