# Molecular Mechanisms Underlying Obesity-related Memory Deficits

> **NIH NIH R01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2020 · $30,888

## Abstract

Project Summary/Abstract
There is a fundamental gap in understanding the molecular mechanisms underlying central nervous system
(CNS) insulin transport. This represents an important gap due to the importance of CNS insulin in memory.
The long-term goal is to understand the impact of obesity on both normal and pathological brain aging. The
objective of this particular application is to investigate the effect of high-fat diet (HFD) induced obesity on CNS
insulin and cognitive function. Obesity-induced effects on CNS insulin transport may render the brain
susceptible to memory impairment. The central hypothesis is that HFD reduces hippocampal insulin transport,
thereby impairing cognitive function. This hypothesis is based on preliminary data produced in the applicant's
laboratory. The rationale for the proposed research is that understanding the impact of CNS insulin on brain
function will set the stage for the development of innovative approaches to mitigate obesity-associated
cognitive decline. Thus, this hypothesis will be tested by pursing two specific aims: 1) test hypothesis that HFD
reduces hippocampal insulin transport and 2) test hypothesis that impairing CNS insulin transport results in
cognitive deficits. Under Aim 1, molecular techniques in HFD mice will be utilized to evaluate the uptake of
insulin into the hippocampus. In addition, the changes in insulin receptor expression and signaling proteins will
be evaluated in isolated hippocampal microvessels, which represent the blood brain barrier. Under the second
aim, a transgenic mouse lacking the insulin receptor specifically in vascular endothelial cells will be used to
evaluate the role of the insulin receptor in CNS insulin transport and the impact on cognitive function. The
approach is innovative, because it utilizes an animal model specifically designed to understand the
mechanisms underlying obesity-related impairments in CNS insulin transport and its impact on cognitive
function. The proposed research is significant, because it is expected it is expected to lead to the development
of targeted therapies to delay or prevent cognitive decline. Ultimately, the results of this work may also be
useful in improving cognitive function associated with neurological disorders such as Mild Cognitive Impairment
or Alzheimer's disease.

## Key facts

- **NIH application ID:** 10109034
- **Project number:** 3R01NS099595-03S1
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Catrina Sims Robinson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $30,888
- **Award type:** 3
- **Project period:** 2017-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10109034

## Citation

> US National Institutes of Health, RePORTER application 10109034, Molecular Mechanisms Underlying Obesity-related Memory Deficits (3R01NS099595-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10109034. Licensed CC0.

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