TY  - JOUR
AU  - Grabrucker, Stefanie
AU  - Pagano, Jessica
AU  - Schweizer, Johanna
AU  - Urrutia-Ruiz, Carolina
AU  - Schön, Michael
AU  - Thome, Kevin
AU  - Ehret, Günter
AU  - Grabrucker, Andreas M
AU  - Zhang, Rong
AU  - Hengerer, Bastian
AU  - Bockmann, Jürgen
AU  - Verpelli, Chiara
AU  - Sala, Carlo
AU  - Böckers, Tobias
TI  - Activation of the medial preoptic area (MPOA) ameliorates loss of maternal behavior in a Shank2 mouse model for autism.
JO  - The EMBO journal
VL  - 40
IS  - 5
SN  - 0261-4189
CY  - Hoboken, NJ [u.a.]
PB  - Wiley
M1  - DZNE-2022-00855
SP  - e104267
PY  - 2021
AB  - 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.
KW  - Animals
KW  - Autistic Disorder: drug therapy
KW  - Autistic Disorder: etiology
KW  - Autistic Disorder: metabolism
KW  - Autistic Disorder: pathology
KW  - Disease Models, Animal
KW  - Female
KW  - Interpersonal Relations
KW  - Male
KW  - Maternal Behavior: drug effects
KW  - Mice
KW  - Mice, Inbred C57BL
KW  - Mice, Knockout
KW  - Nerve Tissue Proteins: physiology
KW  - Piperazines: pharmacology
KW  - Preoptic Area: drug effects
KW  - Preoptic Area: metabolism
KW  - Preoptic Area: pathology
KW  - Synapses
KW  - SHANK3 (Other)
KW  - autism spectrum disorders (Other)
KW  - bonding (Other)
KW  - social behavior (Other)
KW  - synapse (Other)
KW  - DREADD agonist compound 21 (NLM Chemicals)
KW  - Nerve Tissue Proteins (NLM Chemicals)
KW  - Piperazines (NLM Chemicals)
KW  - Shank2 protein, mouse (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:33491217
C2  - pmc:PMC7917557
DO  - DOI:10.15252/embj.2019104267
UR  - https://pub.dzne.de/record/164199
ER  -