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Acrolein induces Alzheimer's disease-like pathologies in vitro and in vivo

Huang, Ying-Juan; Jin, Ming-Hua; Pi, Rong-Biao; Zhang, Jun-Jie; Ouyang, Ying; Chao, Xiao-Juan; Chen, Mei-Hui; Liu, Pei-Qing; Yu, Jian-Chen; Ramassamy, Charles; Dou, Juan; Chen, Xiao-Hong; Jiang, Yi-Ming; Qin, Jian (2013). Acrolein induces Alzheimer's disease-like pathologies in vitro and in vivo Toxicology Letters , vol. 217 , nº 3. p. 184-191. DOI: 10.1016/j.toxlet.2012.12.023.

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Résumé

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.

Type de document:
Mots-clés libres: Acrolein; Alzheimer's disease; Neurotoxicity; Oxidative stress
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 29 mai 2017 16:04
Dernière modification: 29 mai 2017 16:04
URI: http://espace.inrs.ca/id/eprint/2919

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