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@ARTICLE{UrrutiaRuiz:164671,
author = {Urrutia-Ruiz, Carolina and Rombach, Daniel and Cursano,
Silvia and Gerlach-Arbeiter, Susanne and Schoen, Michael and
Bockmann, Juergen and Demestre, Maria and Böckers, Tobias},
title = {{D}eletion of the {A}utism-{A}ssociated {P}rotein {SHANK}3
{A}bolishes {S}tructural {S}ynaptic {P}lasticity after
{B}rain {T}rauma},
journal = {International journal of molecular sciences},
volume = {23},
number = {11},
issn = {1422-0067},
address = {Basel},
publisher = {Molecular Diversity Preservation International},
reportid = {DZNE-2022-01201},
pages = {6081},
year = {2022},
note = {(CC BY)},
abstract = {Autism spectrum disorders (ASDs) are characterized by
repetitive behaviors and impairments of sociability and
communication. About $1\%$ of ASD cases are caused by
mutations of SHANK3, a major scaffolding protein of the
postsynaptic density. We studied the role of SHANK3 in
plastic changes of excitatory synapses within the central
nervous system by employing mild traumatic brain injury
(mTBI) in WT and Shank3 knockout mice. In WT mice, mTBI
triggered ipsi- and contralateral loss of hippocampal
dendritic spines and excitatory synapses with a partial
recovery over time. In contrast, no significant synaptic
alterations were detected in Shank3∆11−/− mice, which
showed fewer dendritic spines and excitatory synapses at
baseline. In line, mTBI induced the upregulation of synaptic
plasticity-related proteins Arc and p-cofilin only in WT
mice. Interestingly, microglia proliferation was observed in
WT mice after mTBI but not in Shank3∆11−/− mice.
Finally, we detected TBI-induced increased fear memory at
the behavioral level, whereas in Shank3∆11−/− animals,
the already-enhanced fear memory levels increased only
slightly after mTBI. Our data show the lack of structural
synaptic plasticity in Shank3 knockout mice that might
explain at least in part the rigidity of behaviors, problems
in adjusting to new situations and cognitive deficits seen
in ASDs. View Full-Text},
keywords = {Animals / Autistic Disorder: genetics / Autistic Disorder:
metabolism / Brain Injuries, Traumatic: metabolism / Mice /
Mice, Knockout / Microfilament Proteins: genetics /
Microfilament Proteins: metabolism / Nerve Tissue Proteins:
genetics / Nerve Tissue Proteins: metabolism / Neuronal
Plasticity: genetics / Synapses: metabolism},
cin = {AG Böckers},
ddc = {540},
cid = {I:(DE-2719)1910002},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pmc = {pmc:PMC9181590},
pubmed = {pmid:35682760},
doi = {10.3390/ijms23116081},
url = {https://pub.dzne.de/record/164671},
}