Gabriel Alberto de Carvalho Barbosa , Marina Prado Rubinho , Milton Kennedy Aquino-Júnior , Jéssica Rodrigues Pedro , Lívia Fligioli Donato , Leonardo Trisciuzzi , Alessandra Oliveira Silva , Silvia Graciela Ruginsk , Carla Speroni Ceron , Nathalia Peixoto , Marcos Vinícios Salles Dias , Marília Gabriella Alves Goulart Pereira
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引用次数: 0
摘要
人们一直在研究肾素血管紧张素系统(RAS)对各种神经系统疾病的影响。在星形胶质细胞中发现了 Ang-(1-7) 和 Ang II 肽的功能受体,突显了这些细胞在中枢神经系统中的生理调节和重要作用。本研究旨在了解 RAS 肽(尤其是 Ang-(1-7) 和 Ang II)在星形胶质细胞分泌营养因子中的作用及其对海马神经元的影响。我们使用了来自 Wistar 株大鼠海马的星形胶质细胞和神经元原代培养物。在本研究中,我们证明了 Ang-(1-7) 对星形胶质细胞的作用,即通过增加 GFAP 的表达诱导反应性星形胶质细胞增生。此外,我们还从用 Ang-(1-7) 处理过的星形胶质细胞中获得了一种条件培养基,这种培养基除了能促进神经元-胶质细胞相互作用所必需的神经营养因子(神经元-胶质细胞相互作用是神经元发生和存活的基础)的分泌外,还对谷氨酸能兴奋毒性具有神经保护作用。反过来,Ang II 对星形胶质细胞的调节作用却不尽相同,从而加剧了对大脑 RAS 的有害影响。神经元与星形胶质细胞之间的相互作用已被证明是 RAS 所介导的中枢效应的一个组成部分,这项研究极大地促进了人们对这一系统运作所涉及的生化机制的理解。
Neuritogenesis and protective effects activated by Angiotensin 1–7 in astrocytes-neuron interaction
The renin angiotensin system (RAS) has been studied for its effects on various neurological disorders. The identification of functional receptors for Ang-(1–7) and Ang II peptides in astrocytes highlights the physiological modulation and the important role of these cells in the central nervous system. The present study aims to understand the role of RAS peptides, particularly Ang-(1–7) and Ang II, in the secretion of trophic factors by astrocytes and their effects on hippocampal neurons. We used primary cultures of astrocytes and neurons from the hippocampus of either sex neonate of Wistar strain rats. In the present study, we demonstrated that the treatment of astrocytes with Ang-(1–7) acts on the modulation of these cells, inducing reactive astrogliosis, identified through the increase in the expression of GFAP. Furthermore, we obtained a conditioned medium from astrocytes treated with Ang-(1–7), which in addition to promoting the secretion of neurotrophic factors essential for neuronal-glial interactions that are fundamental for neuritogenesis and neuronal survival, showed a neuroprotective effect against glutamatergic excitotoxicity. In turn, Ang II does not exhibit the same effects on astrocyte modulation, exacerbating deleterious effects on brain RAS. Neuron-astrocyte interactions have been shown to be an integral part of the central effects mediated by RAS, and this study has significantly contributed to the understanding of the biochemical mechanisms involved in the functioning of this system.
期刊介绍:
The aim of Neuropeptides is the rapid publication of original research and review articles, dealing with the structure, distribution, actions and functions of peptides in the central and peripheral nervous systems. The explosion of research activity in this field has led to the identification of numerous naturally occurring endogenous peptides which act as neurotransmitters, neuromodulators, or trophic factors, to mediate nervous system functions. Increasing numbers of non-peptide ligands of neuropeptide receptors have been developed, which act as agonists or antagonists in peptidergic systems.
The journal provides a unique opportunity of integrating the many disciplines involved in all neuropeptide research. The journal publishes articles on all aspects of the neuropeptide field, with particular emphasis on gene regulation of peptide expression, peptide receptor subtypes, transgenic and knockout mice with mutations in genes for neuropeptides and peptide receptors, neuroanatomy, physiology, behaviour, neurotrophic factors, preclinical drug evaluation, clinical studies, and clinical trials.