SP Transcription factors in psychotic disorders

• Autores: Raquel Pinacho García
• Directores de la Tesis: Josep Maria Haro Abad (dir. tes.), Belén Ramos Josemaría (dir. tes.)
• Lectura: En la Universitat de Barcelona ( España ) en 2015
• Idioma: inglés
• Tribunal Calificador de la Tesis: Juan Carlos Leza Cerro (presid.), María del Mar Mestre (secret.), Andrea Schmitt (voc.)
• Calificación: Sobresaliente Cum Laude
• Materias:
  • Ciencias de la vida
    • Simbiosis
  • Ciencias médicas
    • Psiquiatría
• Enlaces
  • Tesis en acceso abierto en:  TDX  Dipòsit Digital de la UB 
• Resumen

  • Raquel Pinacho García SP TRANSCRIPTION FACTORS IN PSYCHOTIC DISORDERS Abstract Psychotic disorders including bipolar disorder and schizophrenia are a leading cause of disability across the world but the underlying pathophysiological mechanisms remain poorly understood. Moreover, available treatments are inadequate for some sets of symptoms as is the case for negative symptoms in schizophrenia. Alterations in brain connectivity, synaptic plasticity, N-methyl D aspartate receptor (NMDAR) signalling and calcium homeostasis have been suggested to contribute to these disorders. However, the particular transcriptional programmes altered in these disorders are not fully characterised. Previous data suggested that the transcription factors specificity protein 4 (SP4) and SP1 may be involved in the pathophysiology of psychotic disorders. We hypothesized that the expression and/or function of SP4 and SP1 may be altered in psychotic disorders through the regulation of transcriptional programmes involved in neuronal patterning, synaptic plasticity and glutamate signalling. We found that the expression of SP4 and SP1 transcription factors is altered in psychotic disorders. These alterations were mainly found in human postmortem brain of subjects with bipolar disorder and schizophrenia, but also in peripheral mononuclear blood cells in first episode psychosis for SP4 protein. This Thesis also provides data on the regulation of SP proteins by physiological signals in rat neuronal cultures in vitro and in an animal disease model for psychosis in vivo. Together, the results presented in this doctoral Thesis suggest an imbalance in SP4 and SP1 transcription factors in the brains of patients with bipolar disorder and schizophrenia that may contribute to alterations in NMDAR signalling and thereby to the impaired synaptic plasticity and altered brain connectivity observed in psychotic disorders.