# Estrogens, Cardiometabolic Health, and Female Cognitive Aging

> **NIH NIH P01** · TULANE UNIVERSITY OF LOUISIANA · 2024 · $13,328

## Abstract

Project 3 Summary
An unresolved and important question is whether estrogen’s protective effects on the brain and cognition are
attenuated or reversed during diseases such as hypertension. The goal of our overall Program Project is to
address this critical gap using preclinical rodent models of healthy and unhealthy aging to understand
estrogen’s impact on female cognitive aging. The experiments proposed in Project 3 contribute to this goal by
comparing the impact of estrogen on vascular health in models of healthy versus unhealthy aging and
complement the other Research Projects in both concept and approach. Our overall hypothesis is that
cardiovascular disease alters the estrogen receptor profile, disrupting the integration of estrogen’s
molecular signaling pathways and attenuating estrogen’s cardiovascular effects and downstream
protection from Alzheimer’s disease and vascular dementia. Aim 1 will determine the impact of
cardiovascular disease on the vascular response to hormone therapy. This aim utilizes the same middle-aged
Long-Evans rat model of postmenopausal hypertension and cognitive decline as Project 1 led by Dr. Jill Daniel
and builds upon our previous co-authored publication. Aim 2 will establish whether altered estrogen receptor
expression impacts the response to estrogen. These experiments utilize transgenic ERE-luciferase mice along
with mice lacking either ERα or GPER to grasp how cardiovascular disease alters each of these signaling
pathways to reduce estrogen’s protective effects. Aim 3 will assess the impact of hypertension versus arterial
stiffness on female cognition, dendritic plasticity, and neurovascular coupling and determine which
antihypertensive provides the greatest protection to the brain. This aim was designed in collaboration with Co-
Investigator Dr. Ricardo Mostany and utilizes his Thy-1 mouse line to directly assess central mechanisms that
are associated with cognitive decline. The successful completion of the aims proposed in Project 3 will address
critical gaps in our knowledge on the impact of menopausal hormone therapy, enable the development of novel
methods for early detection and prevention of cardiovascular disease-induced cognitive decline, and provide
innovative strategies for improving menopausal hormone pharmacology to protect from Alzheimer’s disease
and vascular dementia.

## Key facts

- **NIH application ID:** 10924711
- **Project number:** 3P01AG071746-02S1
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** JILL M DANIEL
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $13,328
- **Award type:** 3
- **Project period:** 2022-03-01 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10924711

## Citation

> US National Institutes of Health, RePORTER application 10924711, Estrogens, Cardiometabolic Health, and Female Cognitive Aging (3P01AG071746-02S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10924711. Licensed CC0.

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