RESUMO
La esquizofrenia incluye una alteración del juicio de realidad que se caracteriza por la presentación de ideas delirantes que pueden ir acompañadas de alucinaciones de alguna modalidad sensorial. Estos síntomas se presentan en la esquizofrenia, pero también pueden resultar de una amplia variedad de trastornos neurológicos y psiquiátricos. Asimismo, puede ser inducida químicamente. A pesar de que la presentación de psicosis es clínicamente similar, se desconoce si involucra mecanismos neurobiológicos distintos para cada situación. Los pacientes que sufren esquizofrenia no sólo exhiben diversas alteraciones neuroanatómicas sino, además, alteraciones en la neurotransmisión de diferentes sistemas. Actualmente, las teorías más aceptadas proponen una sobreactivación del sistema dopaminérgico y una hipofunción del sistema glutamatérgico. Adicionalmente, otros sistemas involucrados en la fisiopatología de la esquizofrenia son la vía del óxido nítrico, así como los sistemas GABAérgico, glicinérgico y serotonérgico. Más aún, dichos sistemas interactúan entre sí modulando el desarrollo del sistema nervioso y la supervivencia de las células. Las alteraciones descritas en este artículo podrían formar una misma secuencia de eventos. La investigación en este campo habrá de enfocarse en dilucidar esa cadena para acercarse aún más a sus extremos inicial, que le da origen, y final, que tiene implicaciones terapéuticas.
Schizophrenia is a thought disorder characterized by delusional thinking which may be accompanied by hallucinations involving any sensory modality. Schizophrenia may be associated with several neurologic and psychiatric disorders. Also, it may be induced by drugs. In spite of the similarity in psychoses symptomatology, it is unknown if it involves the same underlying neurobiologic mechanisms in those cases. Schizophrenic patients exhibit not only neuroanatomical alterations, but also, distortion of several neurotransmitter systems. Nowadays, the main theories in this regard involve dopaminergic hyperfunction and glutamatergic hypofunction. Additionally, other systems involved in the schizophrenia pathophysiology are the nitric oxide pathway as well as GABAergic, glycinergic and serotonergic systems. Furthermore, those systems interact with each other to modulate nervous system development and cell survival. The alterations described in this paper may be part of a single cascade of events. Research in this field should focus on the elucidation of this chain to find its limits, the initial stage that originates it, and the final stage that has therapeutic implications.
Assuntos
Humanos , Esquizofrenia/fisiopatologia , Esquizofrenia/patologia , Morte Celular , Neurotransmissores/fisiologiaRESUMO
INTRODUCTION: The Egr-1 protein is a transcriptional factor responsive to early growth. Transcriptional regulation of the promoter has been described like responsive to physical stress, osmotic changes, and cellular growth marker. However, there is no report about the pharmacological effect on the transcriptional regulation in gliomas. Hereby we report the modulation of the Egr-1 promoter transcriptional activity induced by the Granulocytes Macrophages Colony Stimulating Factor (GM-CSF) and steroid drugs in human glioma cells (CH235-GM Grade II, U373-GM Grade III, D54-GM Grade IV) using a reporter system transduced by a recombinant adenoviral vector AdEgr-1/luc7. METHODS: Human glioma cells shows with different malignity grade (CH235-GM Grado II; U373-GM Grado III; D54-GM Grado IV) were transduced with no replicative adenoviral vector AdEgr-1/Luc7 and exposed to drugs as progesterone, ß-estradiol and betametasone, and GM-CSF. Transcriptional activity of the egr-1 promoter was quantified by Luciferase reporter gene, cloned downstream to the tata box. Luciferase activity was quantified from whole cell proteins using luminometry assays. RESULTS: U373-GM cell line with GM-CSF, shows an increment on transcriptional activity of Egr-1 promoter, also in endogen way. U373-GM showed a positive regulation of Egr-1, with steroid drugs on the times analyzed. Steroid drugs as progesterone, ß-estradiol and betametasone, shows a pleiotropic behavior on CH235-GM and D54-GM, glioma cell lines. CONCLUSIONS: Inhibition or activation response of Egr-1 promoter shows new framework to explore a mechanism of action of steroid drugs on genetic and epigenetic regulation on tumoral process.