Early-onset Amyloid Deposition and Cognitive Deficits in Transgenic Mice Expressing a Double Mutant Form of Amyloid Precursor Protein 695

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Dehydroepiandrosterone (DHEA) is an anabolic steroid like dihydrotestosterone (DHT), the most potent natural androgen, and tetrahydrogestrinone (THG)

We have recently taken advantage of the unique power of DNA microarrays to compare the genomic expression profile of tetrahydrogestrinone (THG) with that of dihydrotestosterone (DHT), the most potent natural androgen, thus clearly demonstrating that THG is an anabolic steroid. In 2004, the U.S. Controlled Substances Act has been modified to include androstenedione (4-dione) as an anabolic steroid. However, despite the common knowledge that dehydroepiandrosterone (DHEA) is the precursor of testosterone, DHEA has been excluded from the list of anabolic steroids. We thus used the same DNA microarray technology to analyze the expression profile of practically all the 30 000 genes of the mouse genome modulated by DHEA and DHT in classical androgen-sensitive tissues. Daily subcutaneous injections of DHT (0.1 mg) or DHEA (3 mg) for 1 month in gonadectomized C57BL6/129 SV mice increased ventral prostate, dorsal prostate, seminal vesicle and preputial gland weight (p < 0.01 for all tissues). As early as 24 h after single injection of the two steroids, 878, 2681 and 14 probe sets were commonly stimulated or inhibited (p < 0.01, change ≥ 30%), in the prostate (ventral + dorsal), seminal vesicles and preputial glands, respectively, compared to tissues from gonadectomized control animals. After 7 days of daily treatment with DHEA and DHT, 629, 919 and 562 probe sets were commonly modulated in the same tissues while after 27 days of treatment, 1195, 5127 and 2883 probe sets were modulated, respectively. In analogy with the data obtained with THG, the present microarray data provide an extremely precise and unquestionable genomic signature and proof of the androgenic/anabolic activity of DHEA. Such data add to the literature showing that DHEA is transformed into androgens in the human peripheral tissues as well as in laboratory animal species, including the monkey, thus exerting potent androgenic/anabolic activity. The present microarray approach to identify anabolic compounds is applicable to all potential androgenic/anabolic compounds. © 2006 Elsevier Ltd. All rights reserved.Fil: Labrie, Fernand. Laval University; CanadáFil: Luu-The, Van. Laval University; CanadáFil: Martel, Céline. Laval University; CanadáFil: Chernomoretz, Ariel. Laval University; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; ArgentinaFil: Calvo, Ezequiel. Laval University; CanadáFil: Morissette, Jean. Laval University; CanadáFil: Labrie, Claude. Laval University; Canad

Mouse syngenic in vitro blood-brain barrier model: a new tool to examine inflammatory events in cerebral endothelium

Comment in : Technical caveats in identifying the source of endothelial cells in cultures derived from brain microvessels. [Lab Invest. 2005]International audienceAlthough cerebral endothelium disturbance is commonly observed in central nervous system (CNS) inflammatory pathologies, neither the cause of this phenomenon nor the effective participation of blood- brain barrier (BBB) in such diseases are well established. Observations were mostly made in vivo using mouse models of chronic inflammation. This paper presents a new mouse in vitro model suitable for the study of underlying mechanistic events touching BBB functions during CNS inflammatory disturbances. This model consists of a coculture with both primary cell types isolated from mice. Mouse brain capillary endothelial cell (MBCEC)s coming from brain capillaries are in culture with their in vivo partners and form differentiated monolayers that retain endothelial markers and numerous phenotypic properties of in vivo cerebral endothelium, such as: (1) peripheral distribution of tight junction proteins (occludin, claudin-5, claudin-3 and JAM-1); (2) high trans-endothelium electrical resistance value; (3) attenuated paracellular flux of sucrose and inulin; (4) P-gp expression; (5) no MECA-32 expression. Furthermore, this endothelium expresses cell adhesion molecules described in vivo and shows intracellular cell adhesion molecule-1 and vascular cell adhesion molecule-1 upregulation under lipopolysaccharide-treatment. Therefore, this well-differentiated model using autologous cells appears as a suitable support to reconstitute pathological in vitro BBB model