Journal Article

DZNE-2022-00855

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Activation of the medial preoptic area (MPOA) ameliorates loss of maternal behavior in a Shank2 mouse model for autism.

Grabrucker, S. ; Pagano, J. ; Schweizer, J. ; Urrutia-Ruiz, C. ; Schön, M. ; Thome, K. ; Ehret, G. ; Grabrucker, A. M. ; Zhang, R. ; Hengerer, B. ; Bockmann, J. ; Verpelli, C.Extern* ; Sala, C.Extern* ; Böckers, T. (Last author)DZNE*

2021
Wiley Hoboken, NJ [u.a.]

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Please use a persistent id in citations: doi:10.15252/embj.2019104267

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.

Keyword(s): Animals (MeSH) ; Autistic Disorder: drug therapy (MeSH) ; Autistic Disorder: etiology (MeSH) ; Autistic Disorder: metabolism (MeSH) ; Autistic Disorder: pathology (MeSH) ; Disease Models, Animal (MeSH) ; Female (MeSH) ; Interpersonal Relations (MeSH) ; Male (MeSH) ; Maternal Behavior: drug effects (MeSH) ; Mice (MeSH) ; Mice, Inbred C57BL (MeSH) ; Mice, Knockout (MeSH) ; Nerve Tissue Proteins: physiology (MeSH) ; Piperazines: pharmacology (MeSH) ; Preoptic Area: drug effects (MeSH) ; Preoptic Area: metabolism (MeSH) ; Preoptic Area: pathology (MeSH) ; Synapses (MeSH) ; SHANK3 ; autism spectrum disorders ; bonding ; social behavior ; synapse ; DREADD agonist compound 21 ; Nerve Tissue Proteins ; Piperazines ; Shank2 protein, mouse

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Contributing Institute(s):

1. Translational Protein Biochemistry (AG Böckers)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2021

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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