title: Luteolin reduces Alzheimer's disease pathologies induced by traumatic brain injury.
abstract: Traumatic brain injury (TBI) occurs in response to an acute insult to the head and is recognized as a major risk factor for Alzheimer's disease (AD). Indeed, recent studies have suggested a pathological overlap between TBI and AD, with both conditions exhibiting amyloid-beta (Aβ) deposits, tauopathy, and neuroinflammation. Additional studies involving animal models of AD indicate that some AD-related genotypic determinants may be critical factors enhancing temporal and phenotypic symptoms of TBI. Thus in the present study, we examined sub-acute effects of moderate TBI delivered by a gas-driven shock tube device in Aβ depositing Tg2576 mice. Three days later, significant increases in b-amyloid deposition, glycogen synthase-3 (GSK-3) activation, phospho-tau, and pro-inflammatory cytokines were observed. Importantly, peripheral treatment with the naturally occurring flavonoid, luteolin, significantly abolished these accelerated pathologies. This study lays the groundwork for a safe and natural compound that could prevent or treat TBI with minimal or no deleterious side effects in combat personnel and others at risk or who have experienced TBI.
authors.affiliation: James A. Haley Veteran's Administration Hospital, Tampa, FL 33612, USA. dsawmill@health.usf.edu.
authors.forename: Darrell
authors.initials: D
authors.lastname: Sawmiller
authors.affiliation: James A. Haley Veteran's Administration Hospital, Tampa, FL 33612, USA. songli@mail.usf.edu.
authors.forename: Song
authors.initials: S
authors.lastname: Li
authors.affiliation: James A. Haley Veteran's Administration Hospital, Tampa, FL 33612, USA. mshahad@health.usf.edu.
authors.forename: Md
authors.initials: M
authors.lastname: Shahaduzzaman
authors.affiliation: James A. Haley Veteran's Administration Hospital, Tampa, FL 33612, USA. asmith1@health.usf.edu.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Smith
authors.affiliation: James A. Haley Veteran's Administration Hospital, Tampa, FL 33612, USA. dobregon@health.usf.edu.
authors.forename: Demian
authors.initials: D
authors.lastname: Obregon
authors.affiliation: James A. Haley Veteran's Administration Hospital, Tampa, FL 33612, USA. bgiunta@health.usf.edu.
authors.forename: Brian
authors.initials: B
authors.lastname: Giunta
authors.affiliation: James A. Haley Veteran's Administration Hospital, Tampa, FL 33612, USA. cborlong@health.usf.edu.
authors.forename: Cesar V
authors.initials: CV
authors.lastname: Borlongan
authors.affiliation: James A. Haley Veteran's Administration Hospital, Tampa, FL 33612, USA. psanberg@health.usf.edu.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Sanberg
authors.affiliation: James A. Haley Veteran's Administration Hospital, Tampa, FL 33612, USA. jtan@health.usf.edu.
authors.forename: Jun
authors.initials: J
authors.lastname: Tan
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000209:etiology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001930:Brain Injuries / Q000150:complications* / Q000188:drug therapy; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D047311:Luteolin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D014018:Tissue Distribution; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016207:Cytokines; D016875:tau Proteins; D038362:Glycogen Synthase Kinase 3; D047311:Luteolin