Consequences of developmental exposure to concentrated ambient ultrafine particle air pollution combined with the adult paraquat and maneb model of the Parkinson's disease phenotype in male mice

Abstract

Current evidence suggests suceptibility of both the substantia nigra and striatum to exposure to components of air pollution. Further, air pollution has been associated with increased risk of PD diagnsosis in humans or PD-like pathology in animals. This study examined whether exposure of mice to concentrated ambient ultrafine particles (CAPS; <100nm diameter) during the first two weeks of life would alter susceptibility to induction of the Parkinson's disease phenyotype (PDP) in a pesticide-based paraquat and maneb (PQ+MB) model during adulthood utilizing i.p. injections of 10mg/kg PQ and 30mg/kg MB 2× per week for 6 weeks. Evidence of CAPS-induced enhancement of the PQ+MB PDP was limited primarily to delayed recovery of locomotor activity 24 post-injection of PQ+MB that could be related to alterations in striatal GABA inhibitory function. Absence of more extensive interactions might also reflect the finding that CAPS and PQ+MB appeared to differentially target the nigrostriatal dopamine and amino acid systems, with CAPS impacting striatum and PQ+MB impacting dopamine-glutamate function in midbrain; both CAPS and PQ+MB elevated glutamate levels in these specific regions, consistent with potential excitotoxicity. These findings demonstrate the ability of postnatal CAPS to produce locomotor dysfunction and dopaminergic and glutamateric changes, independent of PQ+MB, in brain regions involved in the PDP.

Keywords: Parkinson's disease; Pesticides; Ultrafine Particles.

Figure 1

Mean particle counts (left) and particle mass concentration (right) ± SD for each day of exposure. Mean particle diameter (right) ± SD for each day of exposure.

Figure 2

Horizontal counts, ambulatory counts, jump time, and vertical time of mice treated with Air/Saline, Air/PQ+MB, CAPS/Saline, & CAPS/PQ+MB immediately following PQ+MB injection (top row) and again 24 hours post-injection (bottom row) as measured over the last 6 injections (of a total of 12). PQ+MB indicates main effect of PQ+MB, CAPS indicates main effect of CAPS, and S represents interaction with session. Data reported as Mean ± SE. (n=14=15/treatment group).

Figure 3

Density of TH in the striatum (left) and stereological cell counts of TH+ neurons and nissl positive bodies in the SNpc (right) of mice exposed to Air/Saline, Air/PQ+MB, CAPS/Air, and CAPS/PQ+MB. Data reported as mean ± SE. PQ+MB indicates main effect of PQ+MB, CAPS indicates main effect of CAPS, and CAP × PQ+MB represents statistical interaction between the two treatments. (n=4–5/treatment group).

Figure 4

Monoamine neurotransmitters and metabolites in mice exposed to Air/Saline, Air/PQ+MB, CAPS/Saline, and CAPS/PQ+MB in striatum (left column), midbrain (middle column) and cortex (right column). Data reported as group mean ± SE. DA TO calculated as [DOPAC]/[DA]. Reported in ng neurotransmitter or metabolite/mg protein. CAPS or PQ+MB indicates main effect of CAPS or PQ+MB, respectively. CAPS × PQ+MB indicates statistical interaction of the treatments. * denotes statistical significance from Air/Saline. (n=9–10/treatment group).

Figure 5

Amino acid neurotransmitter levels in indicated brain regions in mice exposed to Air/Saline, Air/PQ+MB, CAPS/Saline, and CAPS/PQ+MB. Data reported as group mean ± SE. DA TO calculated as [DOPAC]/[DA]. Reported in ng neurotransmitter or metabolite/mg protein. CAPS or PQ+MB indicates main effect of CAPS or PQ+MB, respectively. CAPS × PQ+MB indicates statistical interaction of the treatments. * denotes statistical significance from Air/Saline. (n=9–10/treatment group).