RESUMO
Neurodegenerative disorders are undoubtedly an increasing problem in the health sciences, given the increase of life expectancy and occasional vicious life style. Despite the fact that the mechanisms of such diseases are far from being completely understood, a large number of studies that derive from both the basic science and clinical approaches have contributed substantial data in that direction. In this review, it is discussed several frontiers of basic research on Parkinson´s and Alzheimer´s diseases, in which research groups from three departments of the Institute of Biomedical Sciences of the University of São Paulo have been involved in a multidisciplinary effort. The main focus of the review involves the animal models that have been developed to study cellular and molecular aspects of those neurodegenerative diseases, including oxidative stress, insulin signaling and proteomic analyses, among others. We anticipate that this review will help the group determine future directions of joint research in the field and, more importantly, set the level of cooperation we plan to develop in collaboration with colleagues of the Nucleus for Applied Neuroscience Research that are mostly involved with clinical research in the same field.
Os transtornos neurodegenerativos são, sem dúvida, um problema crescente nas ciências da saúde, dado o aumento da expectativa de vida e de estilos de vida pouco saudáveis. Embora os mecanismos de tais doenças ainda estejam longe de ser esclarecidos, vários estudos que derivam tanto da ciência básica quanto de abordagens clínicas contribuíram nessa direção. Na presente revisão, são discutidas linhas de frente da pesquisa básica sobre as doenças de Parkinson e Alzheimer, em que grupos de pesquisas de três departamentos do Instituto de Ciências Biomédicas da Universidade de São Paulo estão envolvidos em um esforço multidisciplinar. O foco principal desta revisão envolve os modelos animais desenvolvidos para se estudar os aspectos celulares e moleculares daquelas doenças neurodegenerativas, incluindo o estresse oxidativo, a sinalização da insulina e as análises proteômicas, dentre outros. Antecipamos que esta revisão irá auxiliar o grupo a determinar as futuras direções da pesquisa conjunta nessa área e, o mais importante, estabelecer o nível de cooperação que planejamos desenvolver juntamente com colegas do Núcleo de Apoio à Pesquisa em Neurociência Aplicada que estão envolvidos com pesquisa clínica na mesma área.
Assuntos
Animais , Humanos , Doença de Alzheimer/metabolismo , Doença de Parkinson/metabolismo , Doença de Alzheimer/etiologia , Biomarcadores/análise , Encéfalo/patologia , Modelos Animais de Doenças , Exercício Físico/fisiologia , NADPH Oxidases/metabolismo , Estresse Oxidativo/fisiologia , Doença de Parkinson/etiologia , Peptídeos/análise , ProteômicaRESUMO
Neurodegenerative disorders are undoubtedly an increasing problem in the health sciences, given the increase of life expectancy and occasional vicious life style. Despite the fact that the mechanisms of such diseases are far from being completely understood, a large number of studies that derive from both the basic science and clinical approaches have contributed substantial data in that direction. In this review, it is discussed several frontiers of basic research on Parkinson's and Alzheimer's diseases, in which research groups from three departments of the Institute of Biomedical Sciences of the University of São Paulo have been involved in a multidisciplinary effort. The main focus of the review involves the animal models that have been developed to study cellular and molecular aspects of those neurodegenerative diseases, including oxidative stress, insulin signaling and proteomic analyses, among others. We anticipate that this review will help the group determine future directions of joint research in the field and, more importantly, set the level of cooperation we plan to develop in collaboration with colleagues of the Nucleus for Applied Neuroscience Research that are mostly involved with clinical research in the same field.
Assuntos
Doença de Alzheimer/metabolismo , Doença de Parkinson/metabolismo , Doença de Alzheimer/etiologia , Animais , Biomarcadores/análise , Encéfalo/patologia , Modelos Animais de Doenças , Exercício Físico/fisiologia , Humanos , NADPH Oxidases/metabolismo , Estresse Oxidativo/fisiologia , Doença de Parkinson/etiologia , Peptídeos/análise , ProteômicaRESUMO
Connexin (Cx) channels and hemichannels are involved in essential processes during nervous system development such as apoptosis, propagation of spontaneous activity and interkinetic nuclear movement. In the first part of this study, we extensively characterized Cx gene and protein expression during retinal histogenesis. We observed distinct spatio-temporal patterns among studied Cx and an overriding, ubiquitous presence of Cx45 in progenitor cells. The role of Cx-mediated communication was assessed by using broad-spectrum (carbenoxolone, CBX) and Cx36/Cx50 channel-specific (quinine) blockers. In vivo application of CBX, but not quinine, caused remarkable reduction in retinal thickness, suggesting changes in cell proliferation/apoptosis ratio. Indeed, we observed a decreased number of mitotic cells in CBX-injected retinas, with no significant changes in the expression of PCNA, a marker for cells in proliferative state. Taken together, our results pointed a pivotal role of Cx45 in the developing retina. Moreover, this study revealed that Cx-mediated communication is essential in retinal histogenesis, particularly in the control of cell proliferation.
