title: LXR activation protects hippocampal microvasculature in very old triple transgenic mouse model of Alzheimer's disease.
abstract: The vascular hypothesis of Alzheimer's disease postulates that disruption of the brain microvasculature is important for the accumulation of amyloid beta and increased neuroinflammation. Liver X Receptor agonist, GW3965, has been demonstrated to successfully modulate neuroinflammation and lipid metabolism in murine models of AD. This is partially due to increased expression of ApoE levels and increased mobility of endothelial progenitor cells. This paper analyzes changes in the neurovascular unit and in astrocytes and microglia markers following oral administration of GW3965 in a very old triple transgenic AD mice (3xTg-AD mice). We found that astrogliosis, but not activation of microglia, decreased in very old (24 months) 3xTg-AD mice treated with GW965. In addition, GW3965 increased LRP1 levels in neuron-like cells and partially restored microvascular morphology by decreasing tortuosity and increasing length as shown by Lectin immunostaining. Interestingly, these changes were associated with decreased Aβ in blood vessels. In conclusion, short-term treatment of 3xTg-AD mice with GW3965 restored microvascular architecture which may be important in the cognitive improvement previously shown.
authors.affiliation: Grupos de Neurociencias y Muerte Celular, Instituto de Genética y Facultad de Medicina, Universidad Nacional de Colombia, Colombia.
authors.forename: Adrián G
authors.initials: AG
authors.lastname: Sandoval-Hernández
authors.affiliation: Grupos de Neurociencias y Muerte Celular, Instituto de Genética y Facultad de Medicina, Universidad Nacional de Colombia, Colombia.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Restrepo
authors.affiliation: Area de Neurobiología Celular y Molecular, Grupo de Neurociencias de Antioquia, Calle 70, No. 52-21, Medellín, Universidad de Antioquia, Colombia.
authors.forename: Gloria P
authors.initials: GP
authors.lastname: Cardona-Gómez
authors.affiliation: Grupos de Neurociencias y Muerte Celular, Instituto de Genética y Facultad de Medicina, Universidad Nacional de Colombia, Colombia. Electronic address: gharboledab@unal.edu.co.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Arboleda
mesh_terms: D000375:Aging; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001565:Benzoates / Q000494:pharmacology; D001596:Benzylamines / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism*; D000071518:Liver X Receptors / Q000819:agonists* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism; D055806:Microvessels / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D001565:Benzoates; D001596:Benzylamines; D015415:Biomarkers; C473027:GW 3965; D005904:Glial Fibrillary Acidic Protein; D000071518:Liver X Receptors; C528900:glial fibrillary astrocytic protein, mouse
keywords: Alzheimer’s disease; GW3965; Liver x receptors; Neuroinflammation; Neurovascular endothelium