Early life air pollution exposures as a risk factor for neurodevelopmental disorders

Ended Project Grant Awarded Last action

Award ID
R35ES031689
Recipient
Awarding agency
Obligated
$14,310,584

Award facts

Assistance listing
93.113 Environmental Health
Completion date
Funding
  • $12,554,172.00 Federal
  • $1,756,412.00 Non-federal
Place of performance
Rochester, NY 14642, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Numerous studies now report associations between air pollution (AP) exposure and neurodevelopmental disorders (ndds), including autism spectrum disorder, schizophrenia, and attention deficit disorder, all of which share numerous features. My studies of early postnatal (human 3RD trimester brain equivalent) inhalation exposures to concentrated ambient ultrafine (UFP, considered the most reactive component of AP) particles (caps) in mice produced numerous neuropathological and behavioral features of these ndds and of their shared hypothesized mechanisms, including male bias, providing biological plausibility for the epidemiological studies. Additionally, caps exposures markedly elevated brain levels of metals and trace elements, including redox metals (FE, CU) as well as s, CA, and AL, findings indicative of brain metal dyshomeostasis. This proposal seeks to test the overarching hypothesis that AP-induced brain metal dyshomeostasis contributes to male- biased NDD phenotypes via production of neuroinflammation and oxidative stress tested in a series of questions designed to accelerate the understanding of mechanisms, and translational relevance of such effects in 5 key integrated questions emanating from these novel, dramatic and unexpected findings: 1) are toxic trace element contaminants of ufps a source of caps-induced NDD phenotypic features, specifically elevated brain FE and s (inhaled FE nanoparticles and/or SO2) both of which are known neurotoxicants via ferroptotic and oxidative stress mechanisms? 2) what accounts for male bias in UFP-induced neurotoxicity? Does IT reflect an earlier colonization of male brain by activated microglia and their interactions with FE uptake? 3) what are the portals of entry of ufps into brain? We utilize the precocial african spiny mouse with its extended gestational period relative to the altricial C57 mouse in which 3RD trimester occurs postnatally and can include nasal and olfactory uptake to determine whether the african spiny mouse might serve as a more relevant human model. 4) how does nanoparticle processing in brain subsequently influence/modulate toxicity and does IT generate toxic or protective mechanisms e.g., alterations in the ferritin cage? 5) does post-mortem brain tissue from humans that had been diagnosed with ndds (neurobiobank) contain exogenous metal nanoparticles as we see, e.g., with FE located within damaged myelin in corpus callosum after caps? These integrated efforts will begin to elaborate mechanisms of AP-induced ndds and associated SEX differences, to define the most relevant mouse model, and to determine the need to regulate air metal levels for public health protection.

Transactions

Action Federal Non-federal Date
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Original award $890,456 $890,456
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Subawards

Subrecipient Amount Awarded
Faraday Energy LLC Early Life Air Pollution Exposures as a Risk Factor for Neurodevelopmental Disorders $271,296
Faraday Energy LLC $270,006

Quick answers

Who received award R35ES031689?

R35ES031689 was awarded to University Of Rochester by National Institute of Environmental Health Sciences (National Institutes of Health) on August 1, 2021.

How much is award R35ES031689 worth?

$14,310,584 has been obligated on R35ES031689: $12,554,172 in federal funding and $1,756,412 in non-federal funding.

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