Deletion of the Autism-Associated Protein SHANK3 Abolishes Structural Synaptic Plasticity after Brain Trauma

• Published in: International journal of molecular sciences Vol. 23; no. 11; p. 6081
• Main Authors: Urrutia-Ruiz, Carolina, Rombach, Daniel, Cursano, Silvia, Gerlach-Arbeiter, Susanne, Schoen, Michael, Bockmann, Juergen, Demestre, Maria, Boeckers, Tobias M
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29-05-2022; MDPI
• Subjects: Animal cognition; Animals; ASD; Autism; Autistic Disorder - genetics; Autistic Disorder - metabolism; Behavior; Brain Injuries, Traumatic - metabolism; Central nervous system; Cofilin; Dendritic spines; Fear; Hippocampus; Localization; Memory; Mice; Mice, Knockout; Microfilament Proteins - genetics; Microfilament Proteins - metabolism; Microglia; Mutation; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neural plasticity; Neuronal Plasticity - genetics; plasticity; Postsynaptic density; Proteins; Rodents; Scaffolding; SHANK3; Synapses; Synapses - metabolism; Synaptic plasticity; TBI; Trauma; Traumatic brain injury; trauma; plasticity; ASD; TBI; synapses; SHANK3
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23116081

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
, 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
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
∆
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
∆
mice. Finally, we detected TBI-induced increased fear memory at the behavioral level, whereas in
∆
animals, the already-enhanced fear memory levels increased only slightly after mTBI. Our data show the lack of structural synaptic plasticity in
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.