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000164671 1001_ $$aUrrutia-Ruiz, Carolina$$b0
000164671 245__ $$aDeletion of the Autism-Associated Protein SHANK3 Abolishes Structural Synaptic Plasticity after Brain Trauma
000164671 260__ $$aBasel$$bMolecular Diversity Preservation International$$c2022
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000164671 520__ $$aAutism spectrum disorders (ASDs) are characterized by repetitive behaviors and impairments of sociability and communication. About 1% of ASD cases are caused by mutations of SHANK3, a major scaffolding protein of the postsynaptic density. We studied the role of SHANK3 in plastic changes of excitatory synapses within the central nervous system by employing mild traumatic brain injury (mTBI) in WT and Shank3 knockout mice. In WT mice, mTBI triggered ipsi- and contralateral loss of hippocampal dendritic spines and excitatory synapses with a partial recovery over time. In contrast, no significant synaptic alterations were detected in Shank3∆11−/− mice, which showed fewer dendritic spines and excitatory synapses at baseline. In line, mTBI induced the upregulation of synaptic plasticity-related proteins Arc and p-cofilin only in WT mice. Interestingly, microglia proliferation was observed in WT mice after mTBI but not in Shank3∆11−/− mice. Finally, we detected TBI-induced increased fear memory at the behavioral level, whereas in Shank3∆11−/− animals, the already-enhanced fear memory levels increased only slightly after mTBI. Our data show the lack of structural synaptic plasticity in Shank3 knockout mice that might explain at least in part the rigidity of behaviors, problems in adjusting to new situations and cognitive deficits seen in ASDs. View Full-Text
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000164671 650_2 $$2MeSH$$aAnimals
000164671 650_2 $$2MeSH$$aAutistic Disorder: genetics
000164671 650_2 $$2MeSH$$aAutistic Disorder: metabolism
000164671 650_2 $$2MeSH$$aBrain Injuries, Traumatic: metabolism
000164671 650_2 $$2MeSH$$aMice
000164671 650_2 $$2MeSH$$aMice, Knockout
000164671 650_2 $$2MeSH$$aMicrofilament Proteins: genetics
000164671 650_2 $$2MeSH$$aMicrofilament Proteins: metabolism
000164671 650_2 $$2MeSH$$aNerve Tissue Proteins: genetics
000164671 650_2 $$2MeSH$$aNerve Tissue Proteins: metabolism
000164671 650_2 $$2MeSH$$aNeuronal Plasticity: genetics
000164671 650_2 $$2MeSH$$aSynapses: metabolism
000164671 7001_ $$0P:(DE-2719)9002203$$aRombach, Daniel$$b1$$udzne
000164671 7001_ $$aCursano, Silvia$$b2
000164671 7001_ $$aGerlach-Arbeiter, Susanne$$b3
000164671 7001_ $$00000-0002-8905-1810$$aSchoen, Michael$$b4
000164671 7001_ $$aBockmann, Juergen$$b5
000164671 7001_ $$aDemestre, Maria$$b6
000164671 7001_ $$0P:(DE-2719)2812855$$aBöckers, Tobias$$b7$$eLast author$$udzne
000164671 770__ $$aNon-genetic Modifiers of Synaptic Plasticity and Neurotransmission in the Central Nervous System (CNS) in Health and Disease
000164671 773__ $$0PERI:(DE-600)2019364-6$$a10.3390/ijms23116081$$gVol. 23, no. 11, p. 6081 -$$n11$$p6081$$tInternational journal of molecular sciences$$v23$$x1422-0067$$y2022
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