# Air Pollution and Male-Biased Psychiatric Disorders

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2020 · $413,995

## Abstract

Abstract
Our studies in mice show that inhaled exposures during development to concentrated ambient ultrafine particle
(UFP) air pollution produces neuropathological and behavioral features common to 3 male-biased disorders,
i.e., schizophrenia (SCZ), autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD),
providing biological plausibility to a growing epidemiological literature linking these disorders to air pollution. In
fact, the observed features in mice are intriguingly similar to those of SCZ. Our studies were not specifically
designed to test these connections. Therefore, the proposed application seeks to determine the specific
contribution of developmental UFP exposures to SCZ and the mechanisms initiating these adverse effects and
their sex-dependency. Aim 1 tests the hypothesis that developmental UFP exposures will produce, in a UFP
concentration-dependent manner, classic as yet unexamined characteristics of SCZ (alterations in cytokine
profiles, reductions in parvalbumin interneurons and synaptic density and altered pre-pulse inhibition). SCZ has
been linked to increased serum copper (Cu), and markedly elevated brain Cu levels in mice were found after
developmental UFP exposure. Excess brain Cu can also produce neurotoxic features consistent with SCZ.
Consequently, Aim 2 tests the hypothesis that elevated Cu contamination in ambient UFP is a specific driver of
the observed SCZ features. Brain microglial colonization and activation is higher in male brain during the
period of our UFP exposures. Given the critical role of microglial activation and inflammation in SCZ, ASD and
ADHD, and the inflammatory and redox properties of AP and of Cu, Aim 3 tests the mechanistic role of
microglial activation as the initiating mechanism of neurotoxicity in males by administration of the microglial
activation inhibitor, minocycline. During adolescence, female brain exhibits greater microglial number/activation
state. Thus, Aim 3 also tests the hypothesis that adolescent UFP exposure will enhance vulnerability of
females. Findings from these studies assist in defining mechanisms for neuropsychiatric disorders and the
basis of their differential vulnerability by sex and a potential need for additional regulation of air pollution for
public health protection.

## Key facts

- **NIH application ID:** 10065880
- **Project number:** 1R01ES032260-01
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Deborah A Cory-Slechta
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $413,995
- **Award type:** 1
- **Project period:** 2020-09-18 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10065880

## Citation

> US National Institutes of Health, RePORTER application 10065880, Air Pollution and Male-Biased Psychiatric Disorders (1R01ES032260-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10065880. Licensed CC0.

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