title: Acrolein induces Alzheimer's disease-like pathologies in vitro and in vivo.
abstract: The pathologic mechanisms of Alzheimer's disease (AD) have not been fully uncovered. Acrolein, a ubiquitous dietary pollutant and by-product of oxidative stress, can induce cytotoxicity in neurons, which might play an important role in the etiology of AD. Here, we examined the effects of Acrolein on the AD pathologies in vitro and in vivo. We found Acrolein induced HT22 cells death in concentration- and time-dependent manners. Interestingly, Acrolein increased proteins' levels of amyloid precursor protein (APP), β-secretase (BACE-1) and the amyloid β-peptide transporter receptor for advanced glycation end products, and decreased A-disintegrin and metalloprotease (ADAM) 10 levels. In vivo, chronic oral exposure to Acrolein (2.5 mg/kg/day by intragastric gavage for 8 weeks) induced mild cognitive declination and pyknosis/atrophy of hippocampal neurons. The activity of superoxide dismutase was down-regulated while the level of malondialdehyde was up-regulated in rat brain. Moreover, Acrolein resulted in activation of astrocytes, up-regulation of BACE-1 in cortex and down-regulation of ADAM-10 in hippocampus and cortex. Taken together, our findings suggest that exposure to Acrolein induces AD-like pathology in vitro and in vivo. Scavenging Acrolein might be beneficial for the therapy of AD.
authors.affiliation: Department of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China.
authors.forename: Ying-Juan
authors.initials: YJ
authors.lastname: Huang
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Jin
authors.forename: Rong-Biao
authors.initials: RB
authors.lastname: Pi
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Ouyang
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Chao
authors.forename: Mei-Hui
authors.initials: MH
authors.lastname: Chen
authors.forename: Pei-Qing
authors.initials: PQ
authors.lastname: Liu
authors.forename: Jian-Chen
authors.initials: JC
authors.lastname: Yu
authors.forename: Charles
authors.initials: C
authors.lastname: Ramassamy
authors.forename: Juan
authors.initials: J
authors.lastname: Dou
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Chen
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Jiang
authors.forename: Jian
authors.initials: J
authors.lastname: Qin
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000171:Acrolein / Q000633:toxicity*; D000544:Alzheimer Disease / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D019483:Disintegrins / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms
chemical_list: D016564:Amyloid beta-Protein Precursor; D019483:Disintegrins; D000171:Acrolein; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins