Different approaches, one target: understanding cellular mechanisms of Parkinson's and Alzheimer's diseases / Abordagens diferentes, um único objetivo: compreender os mecanismos celulares das doenças de Parkinson e de Alzheimer

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.

Neurotransmitter receptor regulation after deafferentation in the visual system

The present study aimed at understanding the regulation of AMPA-type glutamate receptors (GluRs) and nicotinic acetylcholine receptors (nAChRs) during experimentally-induced neurodegeneration in the chick visual system. Immunohistochemistry, in situ hybridization, and RNAse protection techniques were used to verify the expression of GluR and nAChR subunits at several periods after deafferentation, ranging from 1 to 30 days. The results indicate that GluR1 and 2 expression changes in a biphasic way after deafferentation, decreasing after the shortest survival periods (1-4 days) and increasing afterwards. These effects clearly involve regulation of gene expression, as verified by in situ hybridization and RNAse protection. The regulation of the α2, α4, α5, and β2 nAChR subunits after deafferentation, on the other hand, exhibited a pattern that was exactly the opposite, with an early increase followed by a consistent decrease of expression until 30 days postlesion. Furthermore, nAChR changes were not apparently due to gene expression regulation, but instead by up-regulation/ down-regulation at a protein level. These results suggest that neurotransmitter receptors undergo differential plastic changes after deafferentation in the nervous system and contribute data to their possible role in neurodegeneration and neuroprotection processes.

Neurotransmitter regulation of neural development: acetylcholine and nicotinic receptors

Several neurotransmitter systems have been related to developmental processes during the past decade. In this review, we discuss the evidence that the nicotinic acetylcholine receptors could have an additional function during development that may be unrelated to their role in cholinergic neurotransmission in the vertebrate brain. Both temporal expression data and in vitro and in vivo studies with nicotinic agonists and antagonists have provided direct support for a role of nicotinic receptors in neural developmental processes such as neurite outgrowth and differentiation. A similar picture has emerged for other neurotransmitter and receptor systems as well, which generates a new view of neural processes during both development and mature life

Transport of a nicotinic acetylcholine receptor subunit in axonal systems

The effect of neural lesions upon the distribution of a neuronal nicotinic acetylcholine receptor subunit was investigated in the chick nervous system. Following unilateral retinal lesions, the neuropil staining with an antibody against the Beta2 receptor subunit was dramatically reduced or completely eliminated in all retinorecipient structures. Lesions of the lateral spiriform nucleus, a major Beta2 subunit-containing mesencephalic nucleus, produced a marked reduction of neuropil staining in the deeper layers of the tectum, which represent the main target of that nucleus. The present results indicate that the Beta2 subunit is transported in axonal systems, and might therefore constitute presynaptic receptors in some brain areas.