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Environmental air pollution and in utero brain damage: Maternal manganese (Mn) inhalation alters brain development and susceptibility to postnatal brain injury

      Objective

      Components of air pollution may adversely affect prenatal brain development. Manganese (Mn) is an increasingly used performance-enhancing substitute for lead in gasoline worldwide. This study will evaluate possible perinatal brain abnormalities subsequent to prenatal maternal Mn exposure, with or without postnatal injection of methamphetamine, a known neurotoxicant.

      Study design

      Pregnant rats (groups of 6) were nose-only exposed to MnSO4 aerosol for 90 minutes each day for two days (concentration of 0.71 ± 0.04 mg Mn/m3). Total absorbed dose was calculated as 2.3 ug Mn for particles <1um. Exposed and control pups were injected one month after birth with 5 mg/kg methamphetamine intraperitoneally, twice daily over 2.5 consecutive days, and sacrificed 3 days later. Brain structure and histology were evaluated, focusing on internal capsules and axonal projections from various striatal neurotransmitter systems. Five percent of axons in each capsule are dopaminergic.

      Results

      Histologic examination suggested that, relative to controls, lesions developed within the axon capsules in rats only exposed prenatally to Mn. In these rats, the semi-quantitative data revealed no change in axon size or density compared to controls. Prenatally exposed pups receiving both Mn and methamphetamine showed amplified histologic neurodegenerative damage compared to controls (exposed to only Mn or methamphetamine). Compared to rats treated with methamphetamine only, rats receiving Mn plus methamphetamine treatment had smaller capsule radii, decreased capsule density (p<0.05) and reduced number of capsules per unit area, overall supporting amplified histologic neurodegenerative damage compared to controls.

      Conclusion

      In this model of prenatal exposure, by means of maternal nose-only Mn aerosol exposure, 1) prenatal Mn exposure via maternal inhalation alters brain development and 2) amplifies brain damage caused by standard methamphetamine exposure. In utero exposure to Mn via maternal inhalation may alter fetal brain development and amplify adverse effects of other neurotoxicants.