# Effects of Developmental Exposure to Maternal Diet and Exercise on Offspring Cognition

> **NIH NIH F30** · JOHNS HOPKINS UNIVERSITY · 2021 · $50,520

## Abstract

The overarching goal of this proposal is to examine early environmental contributors to cognition by using a
model of maternal diet and exercise during pregnancy to investigate cognitive and hippocampal function in
offspring. The intrauterine and early life environments set the path for the emergence of adult disease. In the
midst of a worldwide obesity epidemic and parallel globalization of the high-fat “Western” diet, understanding
the long-term consequences of a corresponding fetal environment is crucial. Our laboratory has established a
rodent model of maternal high-fat diet (mHFD) exposure during pregnancy and lactation, with adult offspring
displaying hallmark characteristics of both metabolic dysregulation and cognitive impairment despite weaning
onto a standard low-fat diet. The offspring in our model show hippocampal insulin alterations as well. Taken
together with the known association between insulin resistance, metabolic dysregulation, and cognitive decline,
and emerging evidence for the role of insulin in normal hippocampal development, it appears that
developmental disruption of insulin regulation in our mHFD model may be a major mechanism for the observed
metabolic and cognitive phenotypes. Exercise, which has been shown to improve metabolic health, including
insulin dysregulation, as well as cognitive health, is a promising intervention in targeting these phenotypes.
Emerging studies on maternal exercise during pregnancy suggest that gestational exercise exposure
persistently improves cognitive performance and hippocampal architecture of offspring. Gestational exercise
also improves offspring metabolism, and in the setting of mHFD has also been shown to reverse the offspring
MetS-like phenotype, including a correction of insulin dysregulation. Yet to our knowledge, gestational exercise
has not been studied as a potential intervention for the cognitive dysregulation associated with mHFD. I
propose to use a paradigm of voluntary maternal running wheel exercise during gestation that I have
developed and piloted in combination with our established mHFD model to study hippocampally-mediated
cognitive performance, hippocampal morphology, and hippocampal insulin signaling in adult offspring. In Aim
1, I seek to investigate the effects of gestational exercise exposure on mHFD-associated impairment in
offspring hippocampal structure and function. In Aim 2, I seek to elucidate the mechanistic role of insulin
regulation in mHFD-associated hippocampal impairment and its potential amelioration by gestational exercise.
My overall hypothesis is that voluntary maternal exercise will mitigate or reverse the cognitive effects of mHFD
exposure in offspring, and that this reversal will be mechanistically dependent on correction of hippocampal
insulin regulation. The increasing prevalence of maternal overnutrition creates significant clinical and public
health challenges for future generations. By examining the role of maternal exercise in potentially...

## Key facts

- **NIH application ID:** 10248340
- **Project number:** 5F30HD093338-04
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Seva Khambadkone
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $50,520
- **Award type:** 5
- **Project period:** 2018-08-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10248340

## Citation

> US National Institutes of Health, RePORTER application 10248340, Effects of Developmental Exposure to Maternal Diet and Exercise on Offspring Cognition (5F30HD093338-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10248340. Licensed CC0.

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