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Why microglia kill neurons after neural disorders? The friendly fire hypothesis

Neural Regeneration Research 2019年第9期14卷 1499-1502页

作者： walace gomes-leal Laboratory of Experimental Neuroprotection and Neuroregeneration Institute of Biological Sciences Federal University of Para-Brazil

Neuroinflammation plays a fundamental role on the pathophysiology of acute and chronic neural disorders.Microglia activation is a major event following central nervous system inflammation displaying different phenotypes with beneficial and detrimental actions(a Janus face).The reason for this apparent duality is unknown.We have previously shown that following experimental middle cerebral artery occlusion in the rat brain,microglia seem to support and impair adult neurogenesis in the same ischemic striatum.Based on these results,we raised the hypothesis that in the same pathologic environment,gradients of different ligands distributed over different anatomical niches might contribute to both detrimental and beneficial microglial phenotypes.These ligands(“danger signals”)are released by dying cells and bind to microglial receptors in their membranes.Activation of different microglial receptors induces downstream biochemical pathways culminating in a spectrum of microglial phenotypes like M1 and M2 and others.In this paper,we first review the immune functions of microglia and the role of toll-like receptors on the fight against infections.We then briefly revise the dual role of microglia after neural disorders.We then propose a novel hypothesis to explain the Janus face of microglia during the pathophysiology of central nervous system diseases:the“friendly fire hypothesis”.According to this idea“danger signals”or danger associated molecular patterns released by stressed,damaged and/or dying cells during stroke,trauma and other diseases might activate microglial pattern-recognition receptors(i.e.,toll like receptors)or other unidentified receptors normally activated by pathogens.This could activate the same genetic and biochemical machinery used by microglia to fight against pathogens even in the absence of infection.According to this notion,microglia may cause bystander neuronal damage with a kind of blind“friendly fire”,fighting against a non-existing infection during non-infectious disorders,like stroke and trauma

关键词： stroke trauma Alzheimer’s disease neuroinflammation glial cells phenotypes degeneration neuroprotection

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Neurogenesis in the hippocampus of adult humans: controversy “fixed” at last

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Neural Regeneration Research 2019年第11期14卷 1917-1918页

作者： Silene M.A. Lima walace gomes-leal Laboratory of Neurobiology Institute of Biological SciencesFederal University of ParaBelem-ParaBrazil Laboratory of Experimental Neuroprotection and Neuroregeneration Institute of Biological SciencesFederal University of ParaBelem-ParaBrazil

The presence of adult neurogenesis in the mammalian brain has been a theme of intense controversy for a long time since the original report by Altman and Das (1965). The scientific community, for about 30 years, has difficulties to accept that progenitor cells give rise to new neurons in some specific regions of the mammalian adult brain, the neurogenic niches (Kuhn et al., 1996;Doetsch et al., 1997, 1999).

关键词： Neurogenesis hippocampus mammalian brain

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Microglial activation and adult neurogenesis after brain stroke

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Neural Regeneration Research 2021年第3期16卷 456-459页

作者： Ijair R.C.dos Santos Michelle Nerissa C.Dias walace gomes-leal Laboratory of Experimental Neuroprotection and Neuroregeneration Institute of Biological SciencesFederal University of Pará-BrazilBelém-ParáBrazil

The discovery that new neurons are produced in some regions of the adult mammalian brain is a paradigm-shift in neuroscience research.These new-born cells are produced from neuroprogenitors mainly in the subventricular zone at the margin of the lateral ventricle,subgranular zone in the hippocampal dentate gyrus and in the striatum,a component of the basal ganglia,even in humans.In the human hippocampus,neuroblasts are produced even in elderlies.The regulation of adult neurogenesis is a complex phenomenon involving a multitude of molecules,neurotransmitters and soluble factors released by different sources including glial cells.Microglia,the resident macrophages of the central nervous system,are considered to play an important role on the regulation of adult neurogenesis both in physiological and pathological conditions.Following stroke and other acute neural disorders,there is an increase in the numbers of neuroblast production in the neurogenic niches.Microglial activation is believed to display both beneficial and detrimental role on adult neurogenesis after stroke,depending on the activation level and brain location.In this article,we review the scientific evidence addressing the role of microglial activation on adult neurogenesis after ischemia.A comprehensive understanding of the microglial role after stroke and other neural disorders it is an important step for development of future therapies based on manipulation of adult neurogenesis.

关键词： adult neurogenesis hippocampus ischemia microglia neuroinflammation neuroprotection stroke subventricular zone therapy

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寻找完美之旅——新西兰公路骑行探索

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中国自行车 2015年第8期 128-133页

作者： Wade walace Leoric

在壮美的新西兰南岛，我们骑行探索了静谧的公路、湛蓝的湖泊、耸立的山峰，也认识了瓦纳卡（Wanaka）和皇后镇（Queenstown）那些富有趣味的人们，当然更不能忘了他们的啤酒。

关键词：自行车市场品牌生产企业

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Physiological and Biochemical Characterization of JilóSeeds (Solanum gilo) in Different Harvest Times

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American Journal of Plant Sciences 2017年第10期8卷 2569-2595页

作者： Marcus Vinicius Prado Alves Edila Vilela De Resende Von Pinho Heloisa Oliveira Dos Santos Gustavo Costa Prado Alves Rucyan walace Pereira Agriculture Department Federal University of Lavras Lavras Brazil

The evaluation of seed quality during the development process is important for the definition of the moment of harvest. In this context, the objective in this study was to evaluate the quality of Jiló seeds during development through physiological, biochemical and electrophoretic tests of enzymes. Six genetic materials, JIL white, JIL 001, JIL 005, JIL 006, H1 and H2 were used. Fruits were harvested at 35, 40, 45 days after anthesis (DAA). A total of 50% of all fruits harvested at 45 DAA remained at rest for seven days which were labeled as 45 DAAr. The seeds at each maturation stage were extracted from the fruits and evaluated by water content, weight of one thousand seeds, electric conductivity, germination, germination speed index, seedling emergence, and seedling emergence rate index. The chemical composition of the seeds was also evaluated, as well as the expression of the enzymes esterase, isocitrate lyase, malate dehydrogenase, alcohol dehydrogenase, superoxide dismutase, catalase, peroxidase and endo-β-mannanase. The highest values of germination and vigor were found in seeds harvested at 45 DAA and 45 DAAr, mainly for hybrids H1 and H2. The highest values of lipids and proteins and lower carbohydrates were found in the most immature seeds of Jiló. The enzymes analyzed showed higher expression in the initial stages of development, however reduced with the advancement of the maturation stage. Endo-β-mannanase expression increased with seed development. Jiló seeds harvested at 45 DAAr presented the highest of germination and vigor values. This “being” considered as the ideal harvest point.

关键词： Seed Quality Germination Enzyme Harvesting Point Seed Development

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