# Diversity Supplement to Molecular and Cellular Basis of PCB Developmental Neurotoxicity (Mendieta)

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2024 · $21,619

## Abstract

PROJECT SUMMARY
Lower-chlorinated polychlorinated biphenyls (LC-PCBs) are increasingly recognized as a significant risk to
human health, and a primary target of concern is the developing brain. LC-PCBs are the predominant PCB
congener type detected in the serum of pregnant women at increased risk of having a child with a
neurodevelopmental disorder (NDD), and they are widely detected in not only school air but also the serum of
schoolchildren and teachers. The parent grant investigates how CYP-mediated metabolism influences the in
vitro and in vivo effects of LC-PCBs on CREB-dependent neurodevelopmental processes using state-of-the-art
mouse models that express human CYP2A6 or CYP2B6 but not mouse Cyp2a, 2b, 2f2, 2g1, and 2s1 proteins
(Cyp2abfgs-null mice). Preliminary data generated under the parent grant suggests that the LC-PCB, PCB 28,
interferes with axonal and dendritic growth in primary rat cortical neuron-glia co-cultures. This diversity
supplement leverages and extends findings from the parent grant to address the following questions: (1) Does
exposure to PCB 28 cause developmental neurotoxicity (DNT) in vivo, and (2) To what extent does the route of
exposure influence the in vivo DNT of PCB 28, e.g., are different neurotoxic outcomes observed in pups born to
dams exposed to PCB 28 via diet vs. inhalation? To address these questions, the diversity supplement will use
Sprague Dawley rat dams exposed to varying doses of PCB 28 in the diet vs. the air to test the hypothesis that
maternal exposure to PCB 28 causes neurodevelopmental deficits in weanling pups and that the profile of
developmental neurotoxicity differs between inhalation and dietary exposure. This hypothesis will be tested by
addressing the following aims: 1) Characterize the disposition of PCB 28 and metabolites in dams and pups
following inhalational vs. dietary exposure; (2) Determine whether maternal exposure to PCB 28 via inhalation
vs ingestion differentially impacts neurobehavioral outcomes in juvenile rats; and (3) Evaluate the effects of
maternal exposure to PCB 28 via inhalation vs. diet on neurodevelopmental endpoints. The anticipated outcomes
of these research studies include the identification of LC-PCBs as a new class of environmental contaminants
that interfere with neurodevelopment and novel mechanistic data regarding how the route of exposure impacts
PCB DNT. Together with findings from the parent grant, this research will impact public health by providing
critical mechanistic insights regarding risk that LC-PCBs pose to the developing brain and strategies for
mitigating DNT risk in vulnerable subpopulations. The training goals of this Diversity supplement include: (1)
developing the trainee’s knowledge and technical skill set to enable them to successfully conduct research on
environmental influences on neurodevelopmental outcomes; (2) guiding the trainee’s research activity to ensure
the generation of data needed to support their preparation of a competitive...

## Key facts

- **NIH application ID:** 11100414
- **Project number:** 3R01ES014901-13S2
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** HANS-JOACHIM LEHMLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $21,619
- **Award type:** 3
- **Project period:** 2024-08-29 → 2026-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11100414

## Citation

> US National Institutes of Health, RePORTER application 11100414, Diversity Supplement to Molecular and Cellular Basis of PCB Developmental Neurotoxicity (Mendieta) (3R01ES014901-13S2). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11100414. Licensed CC0.

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