# Outcome of Neurological Disorders in Adults Exposed to Moderate Levels of Alcohol in Utero

> **NIH NIH R01** · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · 2024 · $425,297

## Abstract

Project Summary / Abstract
Heavy maternal alcohol consumption during pregnancy is known to interfere with normal fetal development and
is the leading cause of disabilities and premature mortality in children. On the other hand, moderate level of
maternal alcohol consumption (blood alcohol concentration < 0.08%) is thought to be less disruptive to
neurodevelopment. However, it is still unclear whether such moderate prenatal alcohol exposure (PAE) has any
adverse effect on the brain function of the adult offspring. Our preliminary data now indicate that moderate PAE
could lead to depletion of endogenous glutathione (GSH) level in the brain of the adult mice offspring and also
diminish the function of a brain-enriched and neuron-specific tyrosine phosphatase, STEP that has been shown
to be involved in neuroprotection against excitotoxic insults. The preliminary data also provide compelling
evidence that a mild ischemic insult in adult PAE offspring leads to exacerbation of ischemic brain injury and is
associated with up regulation of inflammatory response in the brain. These findings raise the possibility that
moderate PAE has a life-long impact on the antioxidant defense system in the brain of the offspring. The resulting
higher basal level of oxidative stress could compromise the ability of the brain to compensate when exposed to
a neurological insult in later stages of life leading to augmentation of brain damage. To test this novel hypothesis,
in Aim 1 we propose to evaluate the impact of moderate PAE on the synthesis and turnover of GSH, generation
of reactive oxygen species and function of STEP in different brain regions of adult, middle-aged and aged PAE
mice offspring. Our approach will include the non-invasive Electron Paramagnetic Resonance (EPR) imaging
technique and a multitude of molecular and biochemical studies, utilizing both male and female PAE offspring
with age-matched non-PAE control group. The proposed studies in Aim 2 will utilize magnetic resonance imaging
(MRI) and a battery of behavioral tests for noninvasive and longitudinal evaluation of the progression and severity
of ischemic brain damage in adult and aged PAE mice offspring from both sexes. These studies will further
evaluate whether loss of function of STEP could contribute to the exacerbation of ischemic brain injury in PAE
offspring. At the molecular level, the proposed studies in Aim 3 will further delineate the causal link between the
high basal level of oxidative stress and exacerbation of ischemic brain injury in both male and female PAE
offspring. Our approach will utilize flow cytometry, quantitative PCR, immunohistochemical and pharmacological
studies, as well as multiple knockout mice. The proposed research is significant since it will addresse a significant
gap in our knowledge on the life-long health risks of moderate alcohol consumption during pregnancy.

## Key facts

- **NIH application ID:** 10932154
- **Project number:** 5R01AA030309-02
- **Recipient organization:** UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
- **Principal Investigator:** Surojit Paul
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $425,297
- **Award type:** 5
- **Project period:** 2023-09-20 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10932154

## Citation

> US National Institutes of Health, RePORTER application 10932154, Outcome of Neurological Disorders in Adults Exposed to Moderate Levels of Alcohol in Utero (5R01AA030309-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10932154. Licensed CC0.

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