BackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia in the world. Microglia are the innate immune cells of CNS, their proliferation, activation and survival in pathologic and healthy brain have previously been shown to be highly dependent on CSF1R.MethodsHere we investigate the impact of such receptor on AD etiology and microglia. We deleted CSF1R using Cre/Lox system, the knock-out (KO) is restricted to microglia in the APP/PS1 mouse model. We induced the knock-out at 3-month-old, before plaque formation and evaluated both 6 and 8-month-old groups of mice.ResultsOur findings demonstrated that CSF1R KO did not impair microglial survival and proliferation at 6 and 8 months of age in APP cKO compared to their littermate controls groups APPSwe/PS1. We have also shown that cognitive decline is delayed in CSF1R-deleted mice. Ameliorations of AD etiology is associated with a decrease in plaque volume in cortex and hippocampus area. A compensating system seems to take place following the knock-out, since TREM2/β-Catenin and IL-34 expression are significantly increased. Such a compensatory mechanism may promote microglial survival and phagocytosis of Aβ in the brain.ConclusionsOur results provide new insights on the role of CSF1R in microglia and how it interacts with the TREM2/β-Catenin and IL-34 system to clear Aβ and ameliorates the physiopathology of AD.

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia in the world. Microglia are the innate immune cells of CNS, their proliferation, activation and survival in pathologic and healthy brain have previously been shown to be highly dependent on CSF1R. Methods: Here we investigate the impact of such receptor on AD etiology and microglia. We deleted CSF1R using Cre/Lox system, the knock-out (KO) is restricted to microglia in the APP/PS1 mouse model. We induced the knock-out at 3-month-old, before plaque formation and evaluated both 6 and 8-month-old groups of mice. Results: Our findings demonstrated that CSF1R KO did not impair microglial survival and proliferation at 6 and 8 months of age in APP cKO compared to their littermate controls groups APPSwe/PS1. We have also shown that cognitive decline is delayed in CSF1R-deleted mice. Ameliorations of AD etiology is associated with a decrease in plaque volume in cortex and hippocampus area. A compensating system seems to take place following the knock-out, since TREM2/β-Catenin and IL-34 expression are significantly increased. Such a compensatory mechanism may promote microglial survival and phagocytosis of Aβ in the brain. Conclusions: Our results provide new insights on the role of CSF1R in microglia and how it interacts with the TREM2/β-Catenin and IL-34 system to clear Aβ and ameliorates the physiopathology of AD.

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Alliant les disciplines du droit, de l'économie et de la science politique, l'auteur veut, dans le présent article, permettre au lecteur de saisir rapidement les tenants et les aboutissants de la loi Helms-Burton, adoptée en 1996 par les États-Unis en vue d'isoler économiquement Cuba et que l'on dit extra territoriale. Dans la première partie, l'auteur s'emploie à expliquer les causes ayant mené à l'adoption de cette loi et à en décrire les mesures, spécialement celles qui soulèvent l'opposition de la communauté internationale et d'un bon nombre d'Américains. Ensuite, les réactions à la loi seront analysées, plus particulièrement celles du Canada, du Mexique et de l'Union européenne qui se défendent contre cette loi sur les plans diplomatique et légal. C'est là que l'auteur s'attardera sur le débat entourant la validité juridique de la loi Helms-Burton eu égard à l'Accord général sur les tarifs douaniers et le commerce (GATT) et à l'Accord de libre-échange nord-américain (ALENA) et dans lequel, au respect de la liberté de commerce invoquée par leurs principaux partenaires économiques, les États-Unis opposent les impératifs de leur sécurité nationale.By setting up a tri-disciplinary approach combining law, economics and political science, in this paper the author seeks to enable the reader to quickly encompass the innuendoes underlying the American Helms-Burton Act, an extra-territorial piece of legislation passed in 1996 in an effort to further economically isolate Cuba. Initially, the author explains the causes leading up to this legislation and then states its controversial provisions that have indisposed the international community as well as many Americans. Thereafter, he reviews the reactions to the law, especially those of Canada, Mexico and the European Union, all of whom have taken this Act to task both legally and diplomatically. It is on this point that the author delves into the debate surrounding the legal validity of the Helms-Burton Act in light the World Trade Organization's General Agreement on Tariffs and Trade (GATT) and the North American Free Trade Agreement (NAFTA), namely in which the aforementioned nations have invoked respect for free trade and have been met by the United States' premise of the overriding necessities of national security

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