title: Cigarette smoking accelerated brain aging and induced pre-Alzheimer-like neuropathology in rats.
abstract: Cigarette smoking has been proposed as a major risk factor for aging-related pathological changes and Alzheimer's disease (AD). To date, little is known for how smoking can predispose our brains to dementia or cognitive impairment. This study aimed to investigate the cigarette smoke-induced pathological changes in brains. Male Sprague-Dawley (SD) rats were exposed to either sham air or 4% cigarette smoke 1 hour per day for 8 weeks in a ventilated smoking chamber to mimic the situation of chronic passive smoking. We found that the levels of oxidative stress were significantly increased in the hippocampus of the smoking group. Smoking also affected the synapse through reducing the expression of pre-synaptic proteins including synaptophysin and synapsin-1, while there were no changes in the expression of postsynaptic protein PSD95. Decreased levels of acetylated-tubulin and increased levels of phosphorylated-tau at 231, 205 and 404 epitopes were also observed in the hippocampus of the smoking rats. These results suggested that axonal transport machinery might be impaired, and the stability of cytoskeleton might be affected by smoking. Moreover, smoking affected amyloid precursor protein (APP) processing by increasing the production of sAPPβ and accumulation of β-amyloid peptide in the CA3 and dentate gyrus region. In summary, our data suggested that chronic cigarette smoking could induce synaptic changes and other neuropathological alterations. These changes might serve as evidence of early phases of neurodegeneration and may explain why smoking can predispose brains to AD and dementia.
authors.affiliation: Laboratory of Neurodegenerative Diseases, Department of Anatomy, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Yuen-Shan
authors.initials: YS
authors.lastname: Ho
authors.forename: Xifei
authors.initials: X
authors.lastname: Yang
authors.forename: Sze-Chun
authors.initials: SC
authors.lastname: Yeung
authors.forename: Kin
authors.initials: K
authors.lastname: Chiu
authors.forename: Chi-Fai
authors.initials: CF
authors.lastname: Lau
authors.forename: Andrea Wing-Ting
authors.initials: AW
authors.lastname: Tsang
authors.forename: Judith Choi-Wo
authors.initials: JC
authors.lastname: Mak
authors.forename: Raymond Chuen-Chung
authors.initials: RC
authors.lastname: Chang
mesh_terms: D000107:Acetylation; D000375:Aging / Q000473:pathology*; D019588:Aging, Premature / Q000209:etiology / Q000378:metabolism; D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D009410:Nerve Degeneration / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D012907:Smoking / Q000009:adverse effects* / Q000378:metabolism / Q000473:pathology; D013569:Synapses / Q000378:metabolism; D014028:Tobacco Smoke Pollution / Q000009:adverse effects; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; C489131:Mapt protein, rat; D009419:Nerve Tissue Proteins; D014028:Tobacco Smoke Pollution; D014404:Tubulin; D016875:tau Proteins