title: Prenatal minocycline treatment alters synaptic protein expression, and rescues reduced mother call rate in oxytocin receptor-knockout mice.
abstract: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired communication, difficulty in companionship, repetitive behaviors and restricted interests. Recent studies have shown amelioration of ASD symptoms by intranasal administration of oxytocin and demonstrated the association of polymorphisms in the oxytocin receptor (Oxtr) gene with ASD patients. Deficient pruning of synapses by microglial cells in the brain has been proposed as potential mechanism of ASD. Other researchers have shown specific activation of microglial cells in brain regions related to sociality in patients with ASD. Although the roles of Oxtr and microglia in ASD are in the spotlight, the relationship between them remains to be elucidated. In this study, we found abnormal activation of microglial cells and a reduction of postsynaptic density protein PSD95 expression in the Oxtr-deficient brain. Moreover, pharmacological inhibition of microglia during development can alter the expression of PSD95 and ameliorate abnormal mother-infant communication in Oxtr-deficient mice. Our results suggest that microglial abnormality is a potential mechanism of the development of Oxt/Oxtr mediated ASD-like phenotypes.
authors.affiliation: Laboratory of Molecular Biology, Department of Molecular and Cell Biology, Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori-Amamiyamachi, Aoba-ku, Sendai, Miyagi 981-8555, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Miyazaki
authors.affiliation: Laboratory of Molecular Biology, Department of Molecular and Cell Biology, Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori-Amamiyamachi, Aoba-ku, Sendai, Miyagi 981-8555, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hiraoka
authors.affiliation: Laboratory of Molecular Biology, Department of Molecular and Cell Biology, Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori-Amamiyamachi, Aoba-ku, Sendai, Miyagi 981-8555, Japan.
authors.forename: Shizu
authors.initials: S
authors.lastname: Hidema
authors.affiliation: Laboratory of Molecular Biology, Department of Molecular and Cell Biology, Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori-Amamiyamachi, Aoba-ku, Sendai, Miyagi 981-8555, Japan. Electronic address: knishimori@m.tohoku.ac.jp.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Nishimori
mesh_terms: D000818:Animals; D000067877:Autism Spectrum Disorder / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D008297:Male; D008431:Maternal-Fetal Exchange / Q000187:drug effects; D033261:Maternal-Fetal Relations; D018345:Mice, Knockout; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D008911:Minocycline / Q000008:administration & dosage*; D010121:Oxytocin / Q000378:metabolism*; D011247:Pregnancy; D018045:Receptors, Oxytocin / Q000235:genetics / Q000378:metabolism*
chemical_list: C576074:OXTR protein, mouse; D018045:Receptors, Oxytocin; D010121:Oxytocin; D008911:Minocycline
keywords: Autism spectrum disorder; Lateral septal nucleus; Medial amygdaloid nucleus; Microglia; Oxytocin receptor