title: Increased SP4 and SP1 transcription factor expression in the postmortem hippocampus of chronic schizophrenia.
abstract: Altered levels of transcription factor specificity protein 4 (SP4) and 1 (SP1) in the cerebellum, prefrontal cortex and/or lymphocytes have been reported in severe psychiatric disorders, including early psychosis, bipolar disorder, and chronic schizophrenia subjects who have undergone long-term antipsychotic treatments. SP4 transgenic mice show altered hippocampal-dependent psychotic-like behaviours and altered development of hippocampal dentate gyrus. Moreover, NMDAR activity regulates SP4 function. The aim of this study was to investigate SP4 and SP1 expression levels in the hippocampus in schizophrenia, and the possible effect of antipsychotics and NMDAR blockade on SP protein levels in rodent hippocampus. We analysed SP4 and SP1 expression levels in the postmortem hippocampus of chronic schizophrenia (n = 14) and control (n = 11) subjects by immunoblot and quantitative RT-PCR. We tested the effect of NMDAR blockade on SP factors in the hippocampus of mouse treated with an acute dose of MK801. We also investigated the effect of subacute treatments with haloperidol and clozapine on SP protein levels in the rat hippocampus. We report that SP4 protein and both SP4 and SP1 mRNA expression levels are significantly increased in the hippocampus in chronic schizophrenia. Likewise, acute treatment with MK801 increased both SP4 and SP1 protein levels in mouse hippocampus. In contrast, subacute treatment with haloperidol and clozapine did not significantly alter SP protein levels in rat hippocampus. These results suggest that SP4 and SP1 upregulation may be part of the mechanisms deregulated downstream of glutamate signalling pathways in schizophrenia and might be contributing to the hippocampal-dependent cognitive deficits of the disorder.
authors.affiliation: Unitat de recerca, Parc Sanitari Sant Joan de Déu, Fundació Sant Joan de Déu, Universitat de Barcelona, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM. Dr. Antoni Pujadas, 42, 08830 Sant Boi de Llobregat, Barcelona, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Pinacho
authors.affiliation: Instituto de Biomedicina y Biotecnología de Cantabria (CSIC-UC-SODERCAN), Departamento de Fisiología y Farmacología, Universidad de Cantabria, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM. Avda. Cardenal Herrera Oria s/n, 39011, Santander, Spain.
authors.forename: Elsa M
authors.initials: EM
authors.lastname: Valdizán
authors.affiliation: Instituto de Biomedicina y Biotecnología de Cantabria (CSIC-UC-SODERCAN), Departamento de Fisiología y Farmacología, Universidad de Cantabria, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM. Avda. Cardenal Herrera Oria s/n, 39011, Santander, Spain.
authors.forename: Fuencisla
authors.initials: F
authors.lastname: Pilar-Cuellar
authors.affiliation: Iproteos S.L., Baldiri I Reixac, 10, 08028 Barcelona, Spain.
authors.forename: Roger
authors.initials: R
authors.lastname: Prades
authors.affiliation: Iproteos S.L., Baldiri I Reixac, 10, 08028 Barcelona, Spain; Institute for Research in Biomedicine (IRB Barcelona), Baldiri I Reixac, 10, 08028 Barcelona, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Tarragó
authors.affiliation: Unitat de recerca, Parc Sanitari Sant Joan de Déu, Fundació Sant Joan de Déu, Universitat de Barcelona, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM. Dr. Antoni Pujadas, 42, 08830 Sant Boi de Llobregat, Barcelona, Spain.
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Haro
authors.affiliation: Instituto de Neuropatología, IDIBELL-Hospital Universitario de Bellvitge, Universitat de Barcelona, Centro de Investigación Biomédica en Red para enfermedades neurodegenerativas, CIBERNED. Feixa Llarga s/n, 08907 Hospitalet de LLobregat, Barcelona, Spain.
authors.forename: Isidre
authors.initials: I
authors.lastname: Ferrer
authors.affiliation: Unitat de recerca, Parc Sanitari Sant Joan de Déu, Fundació Sant Joan de Déu, Universitat de Barcelona, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM. Dr. Antoni Pujadas, 42, 08830 Sant Boi de Llobregat, Barcelona, Spain. Electronic address: bramos@fsjd.org.
authors.forename: Belén
authors.initials: B
authors.lastname: Ramos
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001344:Autopsy; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012044:Regression Analysis; D012559:Schizophrenia / Q000473:pathology*; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D051706:Sp4 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D018709:Statistics, Nonparametric
chemical_list: D014150:Antipsychotic Agents; D018691:Excitatory Amino Acid Antagonists; D012333:RNA, Messenger; C497124:SP4 protein, human; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; D051706:Sp4 Transcription Factor; D016291:Dizocilpine Maleate
keywords: Hippocampus; Postmortem brain; SP transcription factors; Schizophrenia