title: Maternal alterations in the proteome of the medial prefrontal cortex in rat.
abstract: Proteomic differences between rat dams and control mothers deprived of their pups immediately after delivery were investigated in the medial prefrontal cortex (mPFC). A 2-D DIGE minimal dye technique combined with LC-MS/MS identified 32 different proteins that showed significant changes in expression in the mPFC, of which, 25 were upregulated and 7 were downregulated in dams. The identity of one significantly increased protein, the small heat-shock protein alpha-crystallin B chain (Cryab), was confirmed via Western blot analysis. Alpha-crystallin B chain was distributed in scattered cells in the mPFC, as demonstrated by immunohistochemistry. Furthermore, it was found to be localized in parvalbumin-containing neurons using double labeling. The elevation of its mRNA level in rat dams was also demonstrated via RT-PCR. The functional classification of the altered proteins was conducted using the UniProt and Gene Ontology protein databases. The identified proteins predominantly participate in synaptic transport and plasticity, neuron development, oxidative stress and apoptosis, and cytoskeleton organization. A common regulator and target analysis of these proteins determined using the Elsevier Pathway Studio Platform suggests that protein level changes associated with pup nursing are driven by growth factors and cytokines, while the MAP kinase pathway was identified as a common target. A high proportion of the proteins that were found to be altered in the mPFC are associated with depression.
  
  
  
  The behavior and emotional state of females change robustly when they become mothers. The brain, which governs these changes, may also undergo molecular alterations in mothers. As no proteomics approaches have been applied regarding maternal changes in the brain, we addressed this issue in the mPFC as this brain area is the uppermost cortical center of maternal control and the associated mood changes. The high number of protein-level alterations found between mothers taking care of their litter and those without pups indicates that pup nursing is associated with cortical protein-level changes. Alterations in proteins participating in synaptic transport, plasticity and neuron development suggest neuroplastic changes in the maternal brain. In turn, the relatively high number of altered proteins in the mPFC associated with depression suggests that the physiological effects of the protein-level alterations in the maternal mPFC could promote the incidence of postpartum depression. Cryab, a protein confirmed to be increased during maternal behaviors, was selectively found in parvalbumin cells, which, as fast-spiking interneurons, are associated with depression. The function of Cryab should be further investigated to establish whether it can be used to identify drug targets for future drug development.
authors.affiliation: MTA-ELTE NAP B Laboratory of Molecular and Systems Neurobiology, Department of Physiology and Neurobiology, Institute of Biology, Hungarian Academy of Sciences and Eötvös Loránd University, Budapest, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Völgyi
authors.affiliation: MTA-ELTE NAP B Laboratory of Molecular and Systems Neurobiology, Department of Physiology and Neurobiology, Institute of Biology, Hungarian Academy of Sciences and Eötvös Loránd University, Budapest, Hungary; Laboratory of Proteomics, Institute of Biology, Eötvös Loránd University, Budapest, 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, Institute of Biology, Hungarian Academy of Sciences and Eötvös Loránd University, Budapest, Hungary; Laboratory of Neuromorphology, Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, Hungary.
authors.forename: Éva Rebeka
authors.initials: ÉR
authors.lastname: Szabó
authors.affiliation: Laboratory of Proteomics, Institute of Biology, Eötvös Loránd University, Budapest, Hungary; MTA-ELTE NAP B Neuroimmunology Research Group, Department of Biochemistry, Institute of Biology, Eötvös Loránd University, Budapest, Hungary.
authors.forename: Balázs András
authors.initials: BA
authors.lastname: Györffy
authors.affiliation: Laboratory of Proteomics Research, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Éva
authors.initials: É
authors.lastname: Hunyadi-Gulyás
authors.affiliation: Laboratory of Proteomics Research, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Medzihradszky
authors.affiliation: Laboratory of Proteomics, Institute of Biology, Eötvös Loránd University, Budapest, Hungary; MTA-TTK NAP B MS Neuroproteomics Research Group, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Juhász
authors.affiliation: Laboratory of Proteomics, Institute of Biology, Eötvös Loránd University, Budapest, Hungary; Department of Physiology and Neurobiology, Institute of Biology, Eötvös Loránd University, Budapest, 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, Institute of Biology, Hungarian Academy of Sciences and Eötvös Loránd University, Budapest, Hungary. Electronic address: dobolyia@caesar.elte.hu.
authors.forename: Árpád
authors.initials: Á
authors.lastname: Dobolyi
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001923:Brain Chemistry; D003459:Crystallins / Q000032:analysis; D003863:Depression / Q000503:physiopathology; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D008426:Maternal Deprivation; D008869:Microtubule-Associated Proteins / Q000032:analysis; D017397:Prefrontal Cortex / Q000737:chemistry*; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods; D051381:Rats; D053719:Tandem Mass Spectrometry
chemical_list: D003459:Crystallins; D008869:Microtubule-Associated Proteins; D020543:Proteome; C530883:cryaB protein, rat
keywords: 2-D DIGE; Alpha-crystallin B chain — Cryab; Common regulator and target analysis; Depression; Maternal behavior; Parvalbumin positive GABAergic interneurons; Synaptic transport and plasticity