155437 20240410115727.0 10.1186/s13041-021-00809-3 doi pmid:34167580 pmid pmc:PMC8223320 pmc altmetric:108148199 altmetric DZNE-2021-00643 English 610 Vyas, Yukti 0 In vitro zinc supplementation alters synaptic deficits caused by autism spectrum disorder-associated Shank2 point mutations in hippocampal neurons. London 2021 BioMed Central article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1712661998_12206 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote Autism Spectrum Disorders (ASDs) are neurodevelopmental disorders characterised by deficits in social interactions and repetitive behaviours. ASDs have a strong genetic basis with mutations involved in the development and function of neural circuitry. Shank proteins act as master regulators of excitatory glutamatergic synapses, and Shank mutations have been identified in people with ASD. Here, we have investigated the impact of ASD-associated Shank2 single nucleotide variants (SNVs) at the synaptic level, and the potential of in vitro zinc supplementation to prevent synaptic deficits. Dissociated rat hippocampal cultures expressing enhanced green fluorescent protein (EGFP) tagged Shank2-Wildtype (WT), and ASD-associated Shank2 single nucleotide variants (SNVs: S557N, V717F, and L1722P), were cultured in the absence or presence of 10 μM zinc. In comparison to Shank2-WT, ASD-associated Shank2 SNVs induced significant decreases in synaptic density and reduced the frequency of miniature excitatory postsynaptic currents. These structural and functional ASD-associated synaptic deficits were prevented by chronic zinc supplementation and further support zinc supplementation as a therapeutic target in ASD. 351 - Brain Function (POF4-351) G:(DE-HGF)POF4-351 POF4-351 POF IV 0 Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de Autism Other Glutamatergic synapses Other Shank2 Other Zinc supplementation Other Animals MeSH Animals, Newborn MeSH Autism Spectrum Disorder: genetics MeSH Autism Spectrum Disorder: pathology MeSH Dietary Supplements MeSH Female MeSH Glutamic Acid: metabolism MeSH Hippocampus: pathology MeSH Male MeSH Nerve Tissue Proteins: genetics MeSH Neurons: drug effects MeSH Neurons: metabolism MeSH Neurons: pathology MeSH Point Mutation: genetics MeSH Rats MeSH Synapses: drug effects MeSH Synapses: pathology MeSH Zinc: pharmacology MeSH Jung, Yewon 1 Lee, Kevin 2 Garner, Craig C P:(DE-2719)2810922 3 dzne Montgomery, Johanna M P:(DE-HGF)0 4 10.1186/s13041-021-00809-3 Vol. 14, no. 1, p. 95 PERI:(DE-600)2436057-0 1 95 Molecular brain 14 2021 1756-6606 OpenAccess http://pub.dzne.de/record/155437/files/DZNE-2021-00643.pdf OpenAccess pdfa http://pub.dzne.de/record/155437/files/DZNE-2021-00643.pdf?subformat=pdfa oai:pub.dzne.de:155437 openaire open_access VDB driver dnbdelivery Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 3 P:(DE-2719)2810922 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-351 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Brain Function 0 DE-HGF Gesundheit Erkrankungen des Nervensystems G:(DE-HGF)POF3-340 G:(DE-HGF)POF3-341 G:(DE-HGF)POF3 G:(DE-HGF)POF3-300 G:(DE-HGF)POF Molecular Signaling 0 2021 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2022-11-11 Creative Commons Attribution CC BY (No Version) LIC:(DE-HGF)CCBYNV V:(DE-HGF) DOAJ 2021-05-04 DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2022-11-11 DBCoverage StatID:(DE-HGF)1190 StatID Biological Abstracts 2021-05-04 DBCoverage StatID:(DE-HGF)0600 StatID Ebsco Academic Search 2022-11-11 JCR StatID:(DE-HGF)0100 StatID MOL BRAIN : 2021 2022-11-11 DBCoverage StatID:(DE-HGF)0501 StatID DOAJ Seal 2021-02-14T16:18:41Z WoS StatID:(DE-HGF)0113 StatID Science Citation Index Expanded 2021-05-04 DBCoverage StatID:(DE-HGF)0500 StatID DOAJ 2021-02-14T16:18:41Z DBCoverage StatID:(DE-HGF)0300 StatID Medline 2022-11-11 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2022-11-11 IF < 5 StatID:(DE-HGF)9900 StatID 2022-11-11 OpenAccess StatID:(DE-HGF)0510 StatID Peer Review StatID:(DE-HGF)0030 StatID ASC 2022-11-11 Article Processing Charges StatID:(DE-HGF)0561 StatID 2021-05-04 DBCoverage StatID:(DE-HGF)0160 StatID Essential Science Indicators 2021-05-04 DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2022-11-11 Fees StatID:(DE-HGF)0700 StatID 2021-05-04 I:(DE-2719)1810001 AG Garner Synaptopathy 0 journal VDB UNRESTRICTED I:(DE-2719)1810001 FullTexts