title: Oxytocin in the regulation of social behaviours in medial amygdala-lesioned mice via the inhibition of the extracellular signal-regulated kinase signalling pathway.
abstract: The neuropeptide oxytocin (OXT) has been implicated in the pathophysiology of behavioural deficits among patients with autism spectrum disorder (ASD). However, the molecular mechanisms underlying its role in ASD remain unclear. In the present study, a murine model with ASD-like phenotypes was induced by intra-medial amygdala injection of N-methyl-d-aspartate, and it was used to investigate the role of OXT in behaviour regulation. Behavioural tests were performed to verify the ASD-like phenotypes of N-methyl-d-aspartate-treated mice, and the results showed that mice with bilateral medial amygdala lesions presented significant behavioural deficits, including impaired learning and memory and increased anxiety and depression. We also observed a notably decreased level of OXT in both the plasma and the hypothalamus of medial amygdala-lesioned mice, and the extracellular signal-regulated kinase (ERK) was activated. Further studies demonstrated that the administration of OXT alleviated ASD-like symptoms and significantly inhibited phosphorylation of ERK; the inhibitory effect was similar to that of U0126, an ERK signalling inhibitor. In addition, OXT administration modulated the expression of downstream proteins of the ERK signalling pathway, such as cyclic adenosine monophosphate response element binding and c-fos. Taken together, our data indicate that OXT plays an important role in ameliorating behavioural deficits in an ASD-like mouse model, which was mediated by inhibiting the ERK signalling pathway and its downstream proteins.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhao
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wu
authors.forename: Yu
authors.initials: Y
authors.lastname: Feng
authors.forename: Chuansheng
authors.initials: C
authors.lastname: Zhao
authors.forename: Chaodong
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D000067877:Autism Spectrum Disorder / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects; D002452:Cell Count; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016202:N-Methylaspartate / Q000009:adverse effects; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D010121:Oxytocin / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D010641:Phenotype; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012919:Social Behavior; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; C488222:Shank2 protein, mouse; D010121:Oxytocin; D016202:N-Methylaspartate; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: N-methyl-d-Aspartate; autism spectrum disorder; extracellular signal-regulated kinase; medial amygdala; oxytocin