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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 ¼ 14) and control (n ¼ 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.

Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria

 Autoría: Pinacho R., Valdizán E.M., Pilar-Cuellar F., Prades R., Tarragó T., Haro J.M., Ferrer I., Ramos B.,

 Fuente: Journal of Psychiatric Research, 2014, 58, 189-196

Editorial: Elsevier

 Año de publicación: 2014

Nº de páginas: 8

Tipo de publicación: Artículo de Revista

 DOI: 10.1016/j.jpsychires.2014.08.006

ISSN: 0022-3956,1879-1379

Url de la publicación: https://doi.org/10.1016/j.jpsychires.2014.08.006

Autores/as

PINACHO, RAQUEL

ELSA MARIA VALDIZAN RUIZ

PILAR-CUELLAR, FUENSCILA

PRADES, ROGER

TARRAGO, TERESA

HARO, JOSEP MARÍA

FERRER, ISIDRE

RAMOS, BELÉN