Woodward Nicholas C, Pakbin Payam, Saffari Arian, Shirmohammadi Farimah, Haghani Amin, Sioutas Constantinos, Cacciottolo Mafalda, Morgan Todd E, Finch Caleb E
Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
Department of Civil and Environmental Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA, USA.
Neurobiol Aging. 2017 May;53:48-58. doi: 10.1016/j.neurobiolaging.2017.01.007. Epub 2017 Jan 13.
Traffic-related air pollution (TRAP) is associated with lower cognition and reduced white matter volume in older adults, specifically for particulate matter <2.5-μm diameter (PM). Rodents exposed to TRAP have shown microglial activation and neuronal atrophy. We further investigated age differences of TRAP exposure, with focus on hippocampus for neuritic atrophy, white matter degeneration, and microglial activation. Young- and middle-aged mice (3 and 18 months female C57BL/6J) were exposed to nanoscale-PM (nPM, <0.2 μm diameter). Young mice showed selective changes in the hippocampal CA1 region, with neurite atrophy (-25%), decreased MBP (-50%), and increased Iba1 (+50%), with dentate gyrus relatively unaffected. Exposure to nPM of young mice decreased GluA1 protein (-40%) and increased TNFa mRNA (10×). Older controls had age changes approximating nPM effects on young, with no response to nPM, suggesting an age-ceiling effect. The CA1 selective vulnerability in young mice parallels CA1 vulnerability in Alzheimer's disease. We propose that TRAP-associated human cognitive and white matter changes involve hippocampal responses to nPM that begin at younger ages.
交通相关空气污染（TRAP）与老年人认知能力下降和白质体积减少有关，特别是对于直径<2.5微米的颗粒物（PM）。暴露于TRAP的啮齿动物表现出小胶质细胞激活和神经元萎缩。我们进一步研究了TRAP暴露的年龄差异，重点关注海马体的神经突萎缩、白质变性和小胶质细胞激活。将年轻和中年小鼠（3个月和18个月大的雌性C57BL/6J）暴露于纳米级PM（nPM，直径<0.2微米）。年轻小鼠在海马CA1区表现出选择性变化，神经突萎缩（-25%）、髓鞘碱性蛋白（MBP）减少（-50%）和离子钙结合衔接分子1（Iba1）增加（+50%），齿状回相对未受影响。年轻小鼠暴露于nPM会使谷氨酸受体A1（GluA1）蛋白减少（-40%）并使肿瘤坏死因子α（TNFa）mRNA增加（10倍）。老年对照组的年龄变化与nPM对年轻小鼠的影响相似，对nPM无反应，表明存在年龄上限效应。年轻小鼠中CA1区的选择性易损性与阿尔茨海默病中CA1区的易损性相似。我们提出，TRAP相关的人类认知和白质变化涉及海马体对nPM的反应，这种反应在较年轻时就开始了。
