The Impact of Inhaled Ambient Ultrafine Particulate Matter on Developing Brain: Potential Importance of Elemental Contaminants

Abstract

Epidemiological studies report associations between air pollution (AP) exposures and several neurodevelopmental disorders including autism, attention deficit disorder, and cognitive delays. Our studies in mice of postnatal (human third trimester brain equivalent) exposures to concentrated ambient ultrafine particles (CAPs) provide biological plausibility for these associations, producing numerous neuropathological and behavioral features of these disorders, including male-biased vulnerability. These findings raise questions about the specific components of AP that underlie its neurotoxicity, which our studies suggest could involve trace elements as candidate neurotoxicants. X-ray fluorescence analyses of CAP chamber filters confirm contamination of AP exposures by multiple elements, including iron (Fe) and sulfur (S). Correspondingly, laser ablation inductively coupled plasma mass spectrometry of brains of male mice indicates marked postexposure elevations of Fe and S and other elements. Elevations of brain Fe and S in particular are consistent with potential ferroptotic, oxidative stress, and altered antioxidant capacity-based mechanisms of CAPs-induced neurotoxicity, supported by observations of increased serum oxidized glutathione and increased neuronal cell death in nucleus accumbens with no corresponding significant increase in caspase-3, in male brains following postnatal CAP exposures. Understanding the role of trace element contaminants of particulate matter AP as a source of neurotoxicity is critical for public health protection.

Neurofluids—Deep inspiration, cilia and preloading of the astrocytic network

“…The effect on the brain from long‐term individual exposure to elevated air pollution is an inflammation‐like pathology resembling AD (Herting et al., 2019). This pathology can be detected even in younger individuals, including children, who live in cities with heavy PM pollution (Calderon‐Garciduenas et al., 2018, 2019; Cory‐Slechta et al., 2019; Power et al., 2018). Astrocytes seemed to be the main target of such disturbances (Filous & Silver, 2016) by oxygenic stress induction and ferroptosis (Lewerenz et al., 2018).…”

Maternal Exposure to Local, Source-specific Ambient Air Pollution During Pregnancy and Autism in Children: a Cohort Study From Southern Sweden

“…Suggested biological mechanisms include oxidative stress, in ammation (neuro-in ammation and systemic in ammation), neurotoxicity, and endocrine disruption [27][28][29][30] . Animal models also support developmental neurotoxicity as a plausible pathway 31,32 , and one such study has demonstrated ASD traits in mice following prenatal exposure to diesel exhaust 33 .…”

Effects of air pollution exposure on social behavior: a synthesis and call for research

“…While it has been well-established that long-term exposure to ambient air pollution increases risk of morbidity and mortality from cardiovascular and respiratory disease [ 3 ], there is a growing literature showing that air pollutant exposure also impacts neural function and social-neurobehavioral outcomes in humans [ 4 – 6 ], such as autism spectrum disorder [ 7 – 11 ], bipolar disorder [ 12 ], and depression [ 13 ]. Experimental studies in animal models have supported the epidemiologic evidence, showing that in rodents, inhalation of air pollutants can lead to characteristics of neurodevelopmental and neuropsychiatric disorders [ 14 – 16 ]. Therefore, if exposure to air pollution can affect the incidence or severity of these disorders, even at ambient levels, how might air pollutants affect social behavior more generally?…”