ABSTRACT
Experimental autoimmune encephalomyelitis is a demyelinating disease that causes paralysis in laboratory rats. This condition lacks treatment that reverses damage to the myelin sheaths of neuronal cells. Therefore, in this study, treatment with EPO as a neuroprotective effect was established to evaluate the ERK 1/2 signaling pathway and its participation in the EAE model. EPO was administered in 5000 U/Kg Sprague Dawley rats. U0126 was used as an inhibitor of the ERK 1/2 pathway to demonstrate the possible activation of this pathway in the model. Spinal cord and optic nerve tissues were evaluated using staining techniques such as H&E and the Luxol Fast Blue myelin-specific technique, as well as immunohistochemistry of the ERK 1/2 protein. The EPO-treated groups showed a decrease in cellular sampling in the spinal cord tissues but mainly in the optic nerve, as well as an increase in the expression of the ERK 1/2 protein in both tissues. The findings of this study suggest that EPO treatment reduces cellular death in EAE-induced rats by regulating the ERK pathway.
Subject(s)
Encephalomyelitis, Autoimmune, Experimental , Erythropoietin , MAP Kinase Signaling System , Neuroprotective Agents , Optic Nerve , Rats, Sprague-Dawley , Spinal Cord , Animals , Encephalomyelitis, Autoimmune, Experimental/drug therapy , Encephalomyelitis, Autoimmune, Experimental/metabolism , Encephalomyelitis, Autoimmune, Experimental/pathology , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Erythropoietin/pharmacology , Optic Nerve/drug effects , Optic Nerve/pathology , Optic Nerve/metabolism , Rats , Spinal Cord/metabolism , Spinal Cord/drug effects , Spinal Cord/pathology , MAP Kinase Signaling System/drug effects , Female , Mitogen-Activated Protein Kinase 3/metabolism , Mitogen-Activated Protein Kinase 1/metabolismABSTRACT
Schizophrenia is a heterogeneous disorder of mental symptoms and alterations, characterized by presenting abnormal ideas and perceptions, in which the individual loses contact with reality as a result of a complex neuropsychological disorganization, which affects the affective, intellectual and behavioral functioning; as well as inducing a significant social dysfunction. The etiology of schizophrenia is extremely complex, and is not very clear yet; it is believed to be the result of the combination of genetic factors and the environment. Numerous neurotransmitters have been implicated in this disease, as is the case of dopamine, serotonin and glutamate. The role of the inflammatory process in the pathogenesis of schizophrenia has been postulated, where a prenatal immune "challenge" during the second trimester of pregnancy can be key to the development of the disease. Some of the pro-inflammatory cytokines (TNF-alpha, IL-1beta and IL-6) play a key role in the processes of modulation of the nervous system functions related to affective, emotional and social alterations in subjects with schizophrenia. The mechanisms associated with inflammation and the anti-inflammatory defense system that may be associated with the development of schizophrenia are still unknown. This review was intended to address schizophrenia, in regards to the mechanisms associated with inflammation and the anti-inflammatory defense system in its development.
La esquizofrenia es un trastorno heterogéneo de síntomas y alteraciones mentales, caracterizadas por presentar ideas y percepciones anormales, en el que el individuo pierde contacto con la realidad a consecuencia de una compleja desorganización neuropsicológica, lo cual afecta el funcionamiento afectivo, intelectual y de comportamiento; asimismo, conlleva una disfunción social significativa. La etiología de la esquizofrenia aún no está establecida con claridad. Numerosos neurotransmisores han sido implicados en esta enfermedad, como es el caso de la dopamina, la serotonina y el glutamato. Se ha postulado el papel del proceso inflamatorio en la patogenia de la esquizofrenia, donde un "desafío" inmune prenatal durante el segundo trimestre de la gestación puede ser clave para el desarrollo de la enfermedad. Algunas de las citocinas proinflamatorias (TNF-alfa, IL-1beta e IL-6) juegan un papel clave en los procesos de modulación de las funciones del sistema nervioso relacionadas con alteraciones afectivas, emocionales y sociales en los sujetos con esquizofrenia. Aún se desconocen los mecanismos asociados con la inflamación y el sistema de defensa antiinflamatorio que pudieran intervenir en el desarrollo de la esquizofrenia. Esta revisión tuvo el propósito de tratar sobre la esquizofrenia, en lo que respecta a los mecanismos asociados con la inflamación y el sistema de defensa antiinflamatorio en su desarrollo.