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Brain Struct Funct

Title:		"Male-specific features are reduced in Mecp2-null mice: analyses of vasopressinergic innervation, pheromone production and social behaviour"
Author(s):		Martinez-Rodriguez E; Martin-Sanchez A; Kul E; Bose A; Martinez-Martinez FJ; Stork O; Martinez-Garcia F; Lanuza E; Santos M; Agustin-Pavon C;
Address:		"Unitat Mixta d'Investigacio Neuroanatomia Funcional, Departament de Biologia Cel.lular, Funcional i Antropologia Fisica, Universitat de Valencia, Av. Vicent Andres Estelles, s/n, 46100, Burjassot, Spain. Unitat Mixta d'Investigacio Neuroanatomia Funcional, Unitat Predepartamental de Medicina, Universitat Jaume I de Castello, Castello, Spain. Neurobiology of Behaviour Research Group (GReNeC-NeuroBio), Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain. Neuroscience Research Program, IMIM-Hospital del Mar Research Institute, Barcelona, Spain. Department of Genetics and Molecular Neurobiology, Institute of Biology, and Center for Behavioral Sciences, Otto-von-Guericke University, Magdeburg, Germany. Neurologie, Ammerland-Klinik GmbH, Westerstede, Germany. Department of Genetics and Molecular Neurobiology, Institute of Biology, and Center for Behavioral Sciences, Otto-von-Guericke University, Magdeburg, Germany. mjpsantos@cnc.uc.pt. CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Rua Larga, Faculdade de Medicina, polo I, 2 masculine andar, 3004-504, Coimbra, Portugal. mjpsantos@cnc.uc.pt. Unitat Mixta d'Investigacio Neuroanatomia Funcional, Departament de Biologia Cel.lular, Funcional i Antropologia Fisica, Universitat de Valencia, Av. Vicent Andres Estelles, s/n, 46100, Burjassot, Spain. pavon@uv.es"
Journal Title:		Brain Struct Funct
Year:		2020
Volume:		20200804
Issue:		7
Page Number:		2219 - 2238
DOI:		10.1007/s00429-020-02122-6
ISSN/ISBN:		1863-2661 (Electronic) 1863-2653 (Linking)
Abstract:		"Deficits in arginine vasopressin (AVP) and oxytocin (OT), two neuropeptides closely implicated in the modulation of social behaviours, have been reported in some early developmental disorders and autism spectrum disorders. Mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene are associated to Rett syndrome and other neuropsychiatric conditions. Thus, we first analysed AVP and OT expression in the brain of Mecp2-mutant mice by immunohistochemistry. Our results revealed no significant differences in these systems in young adult Mecp2-heterozygous females, as compared to WT littermates. By contrast, we found a significant reduction in the sexually dimorphic, testosterone-dependent, vasopressinergic innervation in several nuclei of the social brain network and oxytocinergic innervation in the lateral habenula of Mecp2-null males, as compared to WT littermates. Analysis of urinary production of pheromones shows that Mecp2-null males lack the testosterone-dependent pheromone darcin, strongly suggesting low levels of androgens in these males. In addition, resident-intruder tests revealed lack of aggressive behaviour in Mecp2-null males and decreased chemoinvestigation of the intruder. By contrast, Mecp2-null males exhibited enhanced social approach, as compared to WT animals, in a 3-chamber social interaction test. In summary, Mecp2-null males, which display internal testicles, display a significant reduction of some male-specific features, such as vasopressinergic innervation within the social brain network, male pheromone production and aggressive behaviour. Thus, atypical social behaviours in Mecp2-null males may be caused, at least in part, by the effect of lack of MeCP2 over sexual differentiation"
Keywords:		"Aggression/physiology Animals Arginine Vasopressin/*metabolism Behavior, Animal/*physiology Brain/*metabolism Disease Models, Animal Female Intercellular Signaling Peptides and Proteins/genetics/metabolism Male Methyl-CpG-Binding Protein 2/*genetics Mice;neuroscience;"
Notes:		"MedlineMartinez-Rodriguez, Elena Martin-Sanchez, Ana Kul, Emre Bose, Aparajita Martinez-Martinez, Francisco Jose Stork, Oliver Martinez-Garcia, Fernando Lanuza, Enrique Santos, Monica Agustin-Pavon, Carmen eng BFU2016-77691-C2-1-P/Ministerio de Economia y Competitividad/ PROMETEO/2016/076/Conselleria d'Educacio, Investigacio, Cultura i Esport/ UJI-B2016-45/Universitat Jaume I/ 01GM1302/German Federal Ministry of Education and Research/ 01GM1505/German Federal Ministry of Education and Research/ 85/18/Fundacao Bial/ 2/19/FinRett/ Germany 2020/08/05 Brain Struct Funct. 2020 Sep; 225(7):2219-2238. doi: 10.1007/s00429-020-02122-6. Epub 2020 Aug 4"