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@ARTICLE{Vyas:155437,
author = {Vyas, Yukti and Jung, Yewon and Lee, Kevin and Garner,
Craig C and Montgomery, Johanna M},
title = {{I}n vitro zinc supplementation alters synaptic deficits
caused by autism spectrum disorder-associated {S}hank2 point
mutations in hippocampal neurons.},
journal = {Molecular brain},
volume = {14},
number = {1},
issn = {1756-6606},
address = {London},
publisher = {BioMed Central},
reportid = {DZNE-2021-00643},
pages = {95},
year = {2021},
abstract = {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.},
keywords = {Animals / Animals, Newborn / Autism Spectrum Disorder:
genetics / Autism Spectrum Disorder: pathology / Dietary
Supplements / Female / Glutamic Acid: metabolism /
Hippocampus: pathology / Male / Nerve Tissue Proteins:
genetics / Neurons: drug effects / Neurons: metabolism /
Neurons: pathology / Point Mutation: genetics / Rats /
Synapses: drug effects / Synapses: pathology / Zinc:
pharmacology / Autism (Other) / Glutamatergic synapses
(Other) / Shank2 (Other) / Zinc supplementation (Other)},
cin = {AG Garner},
ddc = {610},
cid = {I:(DE-2719)1810001},
pnm = {351 - Brain Function (POF4-351)},
pid = {G:(DE-HGF)POF4-351},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34167580},
pmc = {pmc:PMC8223320},
doi = {10.1186/s13041-021-00809-3},
url = {https://pub.dzne.de/record/155437},
}