# Microglial lysosomes and selective neuronal vulnerability

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2023 · $49,932

## Abstract

Project Summary
Microglial responses to aging are associated with substantive rearrangements in lysosome
abundance, size, subcellular localization, as well as changes in the expression of numerous
genes associated with lysosome function. Our group has recently shown that these microglial
aging phenotypes emerge with pronounced regional specificity, with the ventral tegmental area
(VTA) and substantia nigra pars compacta (SNc) microglia showing these changes by early
middle age. With support from our parent R01, we are working to determine how these changes
in microglial lysosome networks shape synapse-relevant microglial attributes and impact
synapse integrity and neuronal excitability, which have been shown to be robust contributors to
age-associated cognitive decline. The goal of the current diversity supplement is to support the
career advancement of Ms Abigail Gutierrez through postbaccalaureate training and research
aimed at directly probing relationships between microglial lysosome status and cognitive
function in aging mice. During her undergraduate training at UCLA, Ms Gutierrez worked
together with a postdoctoral fellow to develop a reward-based foraging task and showed that
this task is sensitive to subtle changes in reward-based memory in late middle age, wild-type
mice. Continued postbaccalaureate training in the lab will allow Ms Gutierrez to expand her
scientific and professional skills in critical ways toward her goal of entering an MD/PhD program
and becoming an independent physician-scientist. Abigail will gain essential skills in
immunostaining, high resolution confocal microscopy and image analysis by carrying out
immunohistochemistry to analyze microglial lysosomes in behaviorally-characterized young
adult and aging mice. She will learn mouse husbandry, genotyping, and will further expand her
skills in mouse behavior by running cohorts of mice with genetic manipulations of microglial
lysosome status through the reward-based foraging task. Abigail will improve her independence,
writing, and presentation skills through in-person and online classes, assisting with manuscript
preparation, and sharing her research at international conferences. We have assembled an
excellent mentoring team and mapped out milestones that render this period of
postbaccalaureate training similar to a degree-granting masters program. This proposal will
advance the career of an exceptional young scientist and allow her to show whether aging
associated rearrangements in VTA and SNC microglial lysosomes represent a vulnerability in
the aging brain, or a more adaptive response that helps sustain neuronal circuits and cognitive
function later in the lifespan.

## Key facts

- **NIH application ID:** 10829767
- **Project number:** 3R01AG075909-02S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Lindsay Mitchell De Biase
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $49,932
- **Award type:** 3
- **Project period:** 2022-04-01 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10829767

## Citation

> US National Institutes of Health, RePORTER application 10829767, Microglial lysosomes and selective neuronal vulnerability (3R01AG075909-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10829767. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*