Traffic-related air pollution impact on mouse brain accelerates myelin and neuritic aging changes with specificity for CA1 neurons

Abstract

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 (PM2.5). 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 month 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.

Particulate matter and episodic memory decline mediated by early neuroanatomic biomarkers of Alzheimer’s disease

“…regions (Fonken et al, 2011), reduced synaptic function (Ku et al, 2017) in CA1 neurons (Davis et al, 2013), and decreased myelin basic protein in white matter and increased atrophy of neurites in the CA1 region (Woodward et al, 2017) have been observed. These neurotoxicological data collectively suggest that some hippocampal subfields may be more sensitive than others to the adverse PM-effects.…”

An association between air pollution and daily most frequently visits of eighteen outpatient diseases in an industrial city

“…Traffic-related air pollution has shown to trigger microglial activation and neuronal atrophy 11 , and affect embryonic and adult neurons through glutamatergic mechanisms in rodent models 12 . Structural brain magnetic resonance imaging scans revealed that older women with greater PM 2.5 exposures had significantly smaller white…”

Predisposition to Alzheimer’s and Age-Related Brain Pathologies by PM2.5 Exposure: Perspective on the Roles of Oxidative Stress and TRPM2 Channel

“…Such nPM-induced effects on white matter and GluR1 expression in 3-month-old mice were similar to these in 18-month-old mice due to aging. Moreover, in the old mice, nPM exposure induced no further detrimental effect, again indicating an age-ceiling effect (Woodward et al, 2017). Another recent study shows that exposure of female mice to nPM for 10 weeks selectively reduced neurite density in the CA1 region and attenuated the GluR1 expression without effect on the expression of GluR2, NR2A, NR2B, synaptophysin, and PSD95 (Cacciottolo et al, 2017).…”

“…Another study using 8-week-old male mice showed that exposure to PM2.5 (65.7 ± 34.2 µg/m 3 , 6 h per day, and 5 days per week) for 9 months induced synaptic alterations by increasing the expression of postsynaptic density protein 95 (PSD95) without effect on the expression of presynaptic protein synaptophysin (Bhatt et al, 2015). A recent study using 3-month-old mice shows that exposure to ambient nPM (5 h per day and 3 days per week) for 10 weeks caused white matter damage in the CA1 and DG regions of the hippocampus, and suppressed neurite outgrowth in the CA1 region (Woodward et al, 2017). The same study examined the receptors for glutamate, the key excitatory neurotransmitter in the hippocampus.…”