title: Synaptic proteome changes in the hypothalamus of mother rats.
abstract: To establish synaptic proteome changes associated with motherhood, we isolated synaptosome fractions from the hypothalamus of mother rats and non-maternal control females at the 11th postpartum day. Proteomic analysis by two-dimensional differential gel electrophoresis combined with mass spectrometric protein identification established 26 significant proteins, 7 increasing and 19 decreasing protein levels in the dams. The altered proteins are mainly involved in energy homeostasis, protein folding, and metabolic processes suggesting the involvement of these cellular processes in maternal adaptations. The decrease in a significantly altered protein, complement component 1q subcomponent-binding protein (C1qbp) was validated with Western blotting. Furthermore, immunohistochemistry showed its presence in hypothalamic fibers and terminals in agreement with its presence in synaptosomes. We also found the expression of C1qbp in different hypothalamic nuclei including the preoptic area and the paraventricular hypothalamic nucleus at the protein and at the mRNA level using immunohistochemistry and in situ hybridization histochemistry, respectively. Bioinformatical network analysis revealed that cytokines, growth factors, and protein kinases are common regulators, which indicates a complex regulation of the proteome change in mothers. The results suggest that maternal responsiveness is associated with synaptic proteins level changes in the hypothalamus, and that growth factors and cytokines may govern these alterations.
  
  
  
  The period of motherhood is accompanied with several behavioral, neuroendocrine, emotional and metabolic adaptations in the brain. Although it is established that various hypothalamic networks participate in the maternal adaptations of the rodent brain, our knowledge on the molecular background of these alterations remains seriously limited. In the present study, we first determined that the functional alterations of the maternal brain can be detected at the level of the synaptic proteome in the hypothalamus. Independent confirmation of synaptic localization, and also the established decrease in the level of C1qbp protein suggest the validity of the data. Common regulators of altered proteins belonging to the growth factor and cytokine family suggest that the synaptic adaptation is governed by these extracellular signals and future studies should focus on their specific roles. Our study was also the first to describe the expression pattern of C1qbp in the hypothalamus, a protein potentially involved in mitochondrial and neuroimmunological regulations of synaptic plasticity. Its presence in the preoptic area responsible for maternal behaviors and also in the paraventricular hypothalamic and arcuate nuclei regulating hormonal levels suggests that the same proteins may be involved in different aspects of maternal adaptations. The conclusions of the present work contribute to establishing the molecular alterations that determine different maternal adaptations in the brain. Since maternal changes are models of neuronal plasticity in all social interactions, the reported results can affect a wide field of molecular and behavioral neuroscience.
authors.affiliation: MTA-ELTE NAP B Laboratory of Molecular and Systems Neurobiology, Department of Physiology and Neurobiology, Hungarian Academy of Sciences and Eötvös Loránd University, Budapest H-1117, Hungary; Laboratory of Proteomics, Institute of Biology, Eötvös Loránd University, Budapest H-1117, Hungary.
authors.forename: Edina Brigitta
authors.initials: EB
authors.lastname: Udvari
authors.affiliation: MTA-ELTE NAP B Laboratory of Molecular and Systems Neurobiology, Department of Physiology and Neurobiology, Hungarian Academy of Sciences and Eötvös Loránd University, Budapest H-1117, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Völgyi
authors.affiliation: Laboratory of Proteomics, Institute of Biology, Eötvös Loránd University, Budapest H-1117, Hungary; Department of Pharmaceutical Chemistry, University of Vienna, Vienna A-1090, Austria; MTA-TTK NAP MS Neuroproteomics Research Group, Hungarian Academy of Sciences, Budapest H-1117, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Gulyássy
authors.affiliation: MTA-ELTE NAP B Laboratory of Molecular and Systems Neurobiology, Department of Physiology and Neurobiology, Hungarian Academy of Sciences and Eötvös Loránd University, Budapest H-1117, Hungary; Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest H-1117, Hungary.
authors.forename: Diána
authors.initials: D
authors.lastname: Dimén
authors.affiliation: MTA-ELTE NAP B Laboratory of Molecular and Systems Neurobiology, Department of Physiology and Neurobiology, Hungarian Academy of Sciences and Eötvös Loránd University, Budapest H-1117, Hungary; Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest H-1117, Hungary.
authors.forename: Viktor
authors.initials: V
authors.lastname: Kis
authors.affiliation: Laboratory of Neuromorphology, Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest H-1094, Hungary.
authors.forename: János
authors.initials: J
authors.lastname: Barna
authors.affiliation: Laboratory of Neuromorphology, Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest H-1094, Hungary.
authors.forename: Éva Rebeka
authors.initials: ÉR
authors.lastname: Szabó
authors.affiliation: Department of Pharmaceutical Chemistry, University of Vienna, Vienna A-1090, Austria.
authors.forename: Gert
authors.initials: G
authors.lastname: Lubec
authors.affiliation: Laboratory of Proteomics, Institute of Biology, Eötvös Loránd University, Budapest H-1117, Hungary; MTA-TTK NAP MS Neuroproteomics Research Group, Hungarian Academy of Sciences, Budapest H-1117, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Juhász
authors.affiliation: Laboratory of Proteomics, Institute of Biology, Eötvös Loránd University, Budapest H-1117, Hungary; Department of Physiology and Neurobiology, Eötvös Loránd University, Budapest H-1117, Hungary.
authors.forename: Katalin Adrienna
authors.initials: KA
authors.lastname: Kékesi
authors.affiliation: MTA-ELTE NAP B Laboratory of Molecular and Systems Neurobiology, Department of Physiology and Neurobiology, Hungarian Academy of Sciences and Eötvös Loránd University, Budapest H-1117, Hungary; MTA-ELTE Laboratory of Molecular and Systems Neurobiology, Department of Physiology and Neurobiology, Hungarian Academy of Sciences and Eötvös Loránd University, Budapest H-1117, Hungary. Electronic address: dobolyia@caesar.elte.hu.
authors.forename: Árpád
authors.initials: Á
authors.lastname: Dobolyi
mesh_terms: D000818:Animals; D005260:Female; D007031:Hypothalamus / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D049590:Postpartum Period / Q000378:metabolism* / Q000502:physiology; D020543:Proteome / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D009419:Nerve Tissue Proteins; D020543:Proteome
keywords: 2-D DIGE; C1qbp; Common regulator; Lactation; Maternal behavior; Synaptosome