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Table 4 Summary of cognitive effects from in vivo models (19 studies)

From: Air pollution and children’s health—a review of adverse effects associated with prenatal exposure from fine to ultrafine particulate matter

Reference Animal Model PM Source Dose Route Duration Offspring Effects
Suzuki et al. [112] ICR mice Diesel exhaust 171 μg/m3 Inhalation GD2-GD16 (8 h/day) Decreased spontaneous locomotor activity; neurotransmitters (dopamine and noradrenaline) and metabolites were increased in the prefrontal cortex; decreased SLA due to facilitated release of dopamine in the PFC
Allen et al. [55] C57BL/6J mice Ultrafine PM, concentrated ambient particles 40,000-496,000 particles/cm3 Inhalation PND4–7 and PND10–13 (with and without adult exposure over PND56–60) Increased FR response rates and FR resets, as well as enhanced bias for immediate reward.
Davis et al. [79] C57BL/6J mice nPM; < 200 nm 350 μg/m3 Inhalation 5 h/day 3 days/week for 10 weeks (females exposed 7 weeks before conception to 2 days before birth) Impaired cerebral cortex neuron development in vitro; increased depression-like phenotype in tail-suspension test (male); additional nPM exposure promoted pyramidal neuron development
Allen et al. [56] C57BL/6J mice Ultrafine PM, concentrated ambient particles 40,000 to 496,000 particles/cm3 Inhalation PND4–7 and PND10–13 (with and without adult exposure over PND57–59) Impaired short-term memory on the NOR; mechanistically, cortical and hippocampal changes in amino acids raised the potential for excitotoxicity, and persistent glial activation in frontal cortex and corpus callosum of both sexes
Allen et al. [57] C57BL/6J mice Ultrafine PM, concentrated ambient particles 96 μg/m3 Inhalation PND4–7 and PND10–13 (with a group of males getting additional exposure on PND270) Ventriculomegaly in males that persisted through young adulthood; males also showed a decrease in CNS cytokines (whereas females showed an increase); males exposed on PND270, showed changes in CNS neurotransmitters and glial activation across multiple brain regions and increased hippocampal glutamate
Yokota et al. [97] ICR mice Diesel exhaust 90 μg/m3 Inhalation GD2-17 (8 h/day) Increased social isolation-induced territorial aggressive behavior; increased serum testosterone levels; increased dopamine levels in prefrontal cortex and nucleus accumbens; lower serotonin in nucleus accumbens, amygdala, and hypothalamus
Onoda et al. [113] ICR mice CBNP 2.9, 15, 73 μg/mL Intranasal GD5 and GD9 (once/day) Increase in GFAP in cerebral cortex; increase aquaporin-4 in brain parenchyma; increased expression of Flt1, Sox17, Tgfa, Cyr61
Cory-Slechta et al. [59] C57BL/6J mice Ultrafine PM, concentrated ambient particles 45 μg/m3 Inhalation PND4–7 and PND10–13 (4 h/day) Male-specific alterations in learning and memory functions, while females showed alterations in motivational behaviors but not final performance
Klocke et al. [61] B6C3F1 mice Ultrafine PM, concentrated ambient particles 92.69 μg/m3 Inhalation GD0.5-16.5 (6 h/day) Ventriculomegaly; increased corpus callosum area and reduced hippocampal area in both sexes; CC hypermyleination, microglial activation, and reduced total CC microglia in both sexes; increased iron deposition in CC of female offspring
Allen et al. [58] C57BL/6J mice Ultrafine PM, concentrated ambient particles 96 μg/m3 Inhalation PND 4-7 and PND 10-13 (4 h/day for 4 days/week) Induced inflammation/microglial activation; reduced size of corpus callosum; hypomyelination; aberrant white matter development; increased glutamate; increased repetitive and impulsive behavior
Kulas et al. [114] FVB mice PM2.5 46.7 μg/m3 Inhalation Gestation (6 h/day 5 days/week) Deficits in spatial memory; long-term inflammation and neurodegeneration through increased levels of COX2; changes in levels of synaptophysin and Arg1 proteins; changes in the concentration of cytokines in the brain and spleen
Klocke et al. [62] B6C3F1 mice Ultrafine PM, concentrated ambient particles 92.69 μg/m3 Inhalation GD0.5-16.5 (6 h/day) Elevated iron levels in the cerebellum of females; altered cerebellar gene expression; significant enrichment in inflammation and transmembrane transport processes
Kloche et al. [115] B6C3F1 mice Ultrafine PM, concentrated ambient particles 92.69 μg/m3 Inhalation GD0.5-16.5 (6 h/day) Premature maturational shift in number and proportion of total cells and hypermethylation in both sexes; ventriculomegaly in females (possible amelioration of ventriculomegaly in males); alterations in cycling Ki67+/Olig2+ cell number and proportion of total cells in the female corpus collosum; total CC cellularity was slightly elevated in males
Woodward et al. [116] Sprague Dawley rats TRAP 240 μg/m3 Inhalation GD2, through gestation, until 25 weeks of age (5 h/day, 3 days/week) At 5 month males had 70% fewer newly generated neurons in the dentate gyrus (DG) of the hippocampus; microglia were activated in DG/CA1 subfields (35% more Iba1); altered blood-brain-barrier, with a 75% decrease of the tight junction protein ZO-1 in the CA1 layer, and twofold more iron deposits, a marker of microhemorrhages; impaired contextual memory, reduced food- seeking behavior, and increased depressive behaviors
Sobolewski et al. [60] C57BL/6J mice Ultrafine PM, concentrated ambient particles 45 μg/m3 Inhalation PND4–7 and PND10–13 (4 h/day) Decreased serum T concentrations; social nose-to-nose sniff rates with novel males in adulthood; adult T serum concentrations were positively correlated with nose to nose sniff rates
Chang et al. [98] C57BL/6J mice Diesel exhaust 250-500 μg/m3 Inhalation GD0 to PND21 Deficits in all three of the hallmark categories of ASD behavior: reduced social interaction, increased repetitive behavior; reduced or altered communication
Church et al. [63] B6C3 mice Ultrafine PM, concentrated ambient particles 135.8 μg/m3 Inhalation Gestation followed by additional exposures to both dams and their litters from PND2-10 Significantly decreased sociability in both sexes; however, reductions in reciprocal social interaction/increased grooming behavior were only present in males
Cui et al. [117] ICR mice Diesel exhaust particles 0.4 mg/m3 Inhalation GD1.5-GD15.5 (6 h/day) Longer total distance and time in open field test; increased expression of dopamine receptors (Drd1a, Drd2, Drd3, Drd4, Drd5)
Morris-Schaffer et al. [118] C57BL/6J mice Ultrafine elemental carbon 50 μg/m3 Inhalation PND4–7 and 10–13 (4 h/day) No significant difference in anogenital distance, BW, or CNS pathological; no changes in novel object recognition; elevated plus maze performance, FI, or DRL schedule-controlled behavior
  1. GD gestational day, PND postnatal day, FR fixed ratio, NOR novel object recognition, CC corpus callosum