Prenatal air pollution influences neurodevelopment and behavior in autism spectrum disorder by modulating mitochondrial physiology

Abstract

We investigate the role of the mitochondrion, an organelle highly sensitive to environmental agents, in the influence of prenatal air pollution exposure on neurodevelopment and behavior in 96 children with autism spectrum disorder (ASD) [45 with neurodevelopmental regression (NDR); 76% Male; mean (SD) age 10 y 9 m (3 y 9 m)]. Mitochondrial function was assessed using the Seahorse XFe96 in fresh peripheral blood mononuclear cells. Second and third trimester average and maximal daily exposure to fine air particulate matter of diameter ≤2.5 µm (PM2.5) was obtained from the Environmental Protection Agency’s Air Quality System. Neurodevelopment was measured using the Vineland Adaptive Behavior Scale 2nd edition and behavior was assessed using the Aberrant Behavior Checklist and Social Responsiveness Scale. Prenatal PM2.5 exposure influenced mitochondrial respiration during childhood, but this relationship was different for those with (r = 0.25–0.40) and without (r = −0.07 to −0.19) NDR. Mediation analysis found that mitochondrial respiration linked to energy production accounted for 25% (SD = 2%) and 10% (SD = 2%) of the effect of average prenatal PM2.5 exposure on neurodevelopment and behavioral symptoms, respectively. Structural equation models estimated that PM2.5 and mitochondrial respiration accounted for 34% (SD = 4%) and 36% (SD = 3%) of the effect on neurodevelopment, respectively, and that behavior was indirectly influenced by mitochondrial respiration through neurodevelopment but directly influenced by prenatal PM2.5. Our results suggest that prenatal exposure to PM2.5 disrupts neurodevelopment and behavior through complex mechanisms, including long-term changes in mitochondrial respiration and that patterns of early development need to be considered when studying the influence of environmental agents on neurodevelopmental outcomes.

Mitochondria May Mediate Prenatal Environmental Influences in Autism Spectrum Disorder

“…The prenatal Cu to Zn ratio was associated with two independent measures of language development in all children with ASD (both those with and without NDR) [ 29 ]. This latter study extends previous findings linking prenatal nutrient metal (Zn, Mn, Cu) exposure and ASD [ 26 , 27 , 124 , 125 , 126 , 127 ].…”

“…Abnormalities in several nutrient metals have been linked to an increased risk of ASD. Studies have associated an increased risk of ASD with atypical pre- and postnatal Zn and Cu metabolism [ 26 ] and found that atypical levels of essential (Zn, Mn) and non-essential (Pb) metals during prenatal development and early life in individuals with ASD are associated with long-term physiological and developmental alternations [ 27 ]. Studies have associated low maternal iron (Fe) with increased ASD risk [ 28 ].…”

“…The relationship was significantly different for those children with and without a history of NDR. For those with a history of NDR, higher prenatal PM 2.5 exposure was associated with higher mitochondrial respiration rates, while for those without a history of NDR, higher prenatal PM 2.5 exposure was related to lower mitochondrial respiration [ 27 ]. Additional research has linked prenatal air pollution exposure to mitochondrial-derived peptides in cord blood that are associated with long-term changes in mitochondrial physiology [ 50 ].…”

An mtDNA mutant mouse demonstrates that mitochondrial deficiency can result in autism endophenotypes

“…Reciprocally, the nucleus regulates the mitochondrion via an array of transcription factors ( 50 ). Hence, partial mitochondrial defects caused by hemizygous mutations, modulated by background mtDNA variation ( 25 ) and environmental challenge ( 51 , 52 ), could cause similar mitochondrial defects to that of the ND6 P25L mouse.…”

Recent Advances in Self-Powered Electrochemical Systems

“…Air pollution including fine air particulate matter (PM) and gaseous pollutants is a crucial toxicant caused by human activities. Generally, air pollution exposure is related to lots of chronic diseases, such as pulmonary and cardiovascular disease [ 62 ]. To clean PM 2.5, Guo et al reported an SP triboelectric negative air ion generator (MSNG) powered by TENG [ 63 ].…”