title: Proteomic analyses of limbic regions in neonatal male, female and androgen receptor knockout mice.
abstract: It is well-established that organizational effects of sex steroids during early development are fundamental for sex-typical displays of, for example, mating and aggressive behaviors in rodents and other species. Male and female brains are known to differ with respect to neuronal morphology in particular regions of the brain, including the number and size of neurons, and the density and length of dendrites in nuclei of hypothalamus and amygdala. The aim of the present study was to use global proteomics to identify proteins differentially expressed in hypothalamus/amygdala during early development (postnatal day 8) of male, female and conditional androgen receptor knockout (ARNesDel) male mice, lacking androgen receptors specifically in the brain. Furthermore, verification of selected sexually dimorphic proteins was performed using targeted proteomics.
  
  
  
  Our proteomic approach, iTRAQ, allowed us to investigate expression differences in the 2998 most abundantly expressed proteins in our dissected tissues. Approximately 170 proteins differed between the sexes, and 38 proteins between ARNesDeland control males (p < 0.05). In line with previous explorative studies of sexually dimorphic gene expression we mainly detected subtle protein expression differences (fold changes <1.3). The protein MARCKS (myristoylated alanine rich C kinase substrate), having the largest fold change of the proteins selected from the iTRAQ analyses and of known importance for synaptic transmission and dendritic branching, was confirmed by targeted proteomics as differentially expressed between the sexes.
  
  
  
  Overall, our results provide solid evidence that a large number of proteins show sex differences in their brain expression and could potentially be involved in brain sexual differentiation. Furthermore, our finding of a sexually dimorphic expression of MARCKS in the brain during development warrants further investigation on the involvement in sexual differentiation of this protein.
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, POB 431, 405 30, Göteborg, Sweden.|Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Zettergren
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, POB 431, 405 30, Göteborg, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Karlsson
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, POB 431, 405 30, Göteborg, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Studer
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, POB 431, 405 30, Göteborg, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Sarvimäki
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.|Department of Neuropathology, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK.
authors.forename: Petronella
authors.initials: P
authors.lastname: Kettunen
authors.affiliation: The Proteomics Core Facility, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
authors.forename: Annika
authors.initials: A
authors.lastname: Thorsell
authors.affiliation: The Proteomics Core Facility, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
authors.forename: Carina
authors.initials: C
authors.lastname: Sihlbom
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, POB 431, 405 30, Göteborg, Sweden. lars.westberg@pharm.gu.se.
authors.forename: Lars
authors.initials: L
authors.lastname: Westberg
mesh_terms: D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D005260:Female; D007031:Hypothalamus / Q000378:metabolism*; D008032:Limbic System / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D040901:Proteomics; D011944:Receptors, Androgen / Q000235:genetics*; D012727:Sex Characteristics
chemical_list: D011944:Receptors, Androgen
keywords: Amygdala; Androgen receptor; Hypothalamus; Neonatal; Proteomics; Sex differences