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Levetiracetam reverses synaptic deficits produced by overexpression of SV2A.

التفاصيل البيبلوغرافية
العنوان: Levetiracetam reverses synaptic deficits produced by overexpression of SV2A.
المؤلفون: Amy Nowack, Erik B Malarkey, Jia Yao, Adam Bleckert, Jessica Hill, Sandra M Bajjalieh
المصدر: PLoS ONE, Vol 6, Iss 12, p e29560 (2011)
بيانات النشر: Public Library of Science (PLoS), 2011.
سنة النشر: 2011
المجموعة: LCC:Medicine
LCC:Science
مصطلحات موضوعية: Medicine, Science
الوصف: Levetiracetam is an FDA-approved drug used to treat epilepsy and other disorders of the nervous system. Although it is known that levetiracetam binds the synaptic vesicle protein SV2A, how drug binding affects synaptic functioning remains unknown. Here we report that levetiracetam reverses the effects of excess SV2A in autaptic hippocampal neurons. Expression of an SV2A-EGFP fusion protein produced a ∼1.5-fold increase in synaptic levels of SV2, and resulted in reduced synaptic release probability. The overexpression phenotype parallels that seen in neurons from SV2 knockout mice, which experience severe seizures. Overexpression of SV2A also increased synaptic levels of the calcium-sensor protein synaptotagmin, an SV2-binding protein whose stability and trafficking are regulated by SV2. Treatment with levetiracetam rescued normal neurotransmission and restored normal levels of SV2 and synaptotagmin at the synapse. These results indicate that changes in SV2 expression in either direction impact neurotransmission, and suggest that levetiracetam may modulate SV2 protein interactions.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1932-6203
Relation: http://europepmc.org/articles/PMC3248421?pdf=render; https://doaj.org/toc/1932-6203
DOI: 10.1371/journal.pone.0029560
URL الوصول: https://doaj.org/article/165d6cc039d741cdbf25149912642200
رقم الأكسشن: edsdoj.165d6cc039d741cdbf25149912642200
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:19326203
DOI:10.1371/journal.pone.0029560