1. Activation of the medial preoptic area (MPOA) ameliorates loss of maternal behavior in a Shank2 mouse model for autism
- Author
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Kevin Thome, Carolina Urrutia-Ruiz, Stefanie Grabrucker, Carlo Sala, Günter Ehret, Johanna Schweizer, Andreas M. Grabrucker, Tobias M. Boeckers, Michael Schön, Rong Zhang, Juergen Bockmann, Bastian Hengerer, Jessica Pagano, Chiara Verpelli, European Union (EU), and Horizon 2020
- Subjects
Male ,pathology [Preoptic Area] ,Autismus ,bonding ,Piperazines ,Synapse ,Mice ,0302 clinical medicine ,Postsynaptic potential ,Social behavior ,Autism spectrum disorder ,Maternal Behavior ,metabolism [Autistic Disorder] ,SHANK3 ,Mice, Knockout ,0303 health sciences ,General Neuroscience ,DREADD agonist compound 21 ,Cognition ,Articles ,SHANK2 ,medicine.anatomical_structure ,Hypothalamus ,etiology [Autistic Disorder] ,Excitatory postsynaptic potential ,Female ,physiology [Nerve Tissue Proteins] ,drug effects [Preoptic Area] ,autism spectrum disorders ,Central nervous system ,Shank2 protein, mouse ,Nerve Tissue Proteins ,Biology ,pharmacology [Piperazines] ,drug effects [Maternal Behavior] ,Article ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,ddc:570 ,medicine ,Sozialverhalten ,Animals ,Interpersonal Relations ,ddc:610 ,Autistic Disorder ,Molecular Biology ,030304 developmental biology ,drug therapy [Autistic Disorder] ,General Immunology and Microbiology ,medicine.disease ,Preoptic Area ,Mice, Inbred C57BL ,Disease Models, Animal ,pathology [Autistic Disorder] ,Synapses ,metabolism [Preoptic Area] ,Autism ,Neuroscience ,DDC 610 / Medicine & health ,030217 neurology & neurosurgery - Abstract
Impairments in social relationships and awareness are features observed in autism spectrum disorders (ASDs). However, the underlying mechanisms remain poorly understood. Shank2 is a high���confidence ASD candidate gene and localizes primarily to postsynaptic densities (PSDs) of excitatory synapses in the central nervous system (CNS). We show here that loss of Shank2 in mice leads to a lack of social attachment and bonding behavior towards pubs independent of hormonal, cognitive, or sensitive deficits. Shank2���/��� mice display functional changes in nuclei of the social attachment circuit that were most prominent in the medial preoptic area (MPOA) of the hypothalamus. Selective enhancement of MPOA activity by DREADD technology re���established social bonding behavior in Shank2���/��� mice, providing evidence that the identified circuit might be crucial for explaining how social deficits in ASD can arise., publishedVersion
- Published
- 2021
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