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