# Heterogeneity of mitral cell properties determined by the timing of neurogenesis - Supplement

> **NIH NIH R01** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2021 · $408,829

## Abstract

ABSTRACT
Impaired sense of smell is one of the early symptoms of Alzheimer’s disease (AD). Interestingly, brain areas
involved in olfactory information processing, such as the olfactory bulb (OB), show amyloid-beta (Aβ) deposit
and aggregation of phosphorylated tau at the very early stages of AD. However, the underlying mechanisms of
olfactory dysfunction and the development of these AD pathological hallmarks in the olfactory area are still largely
unknown. In the proposed research, we will focus on the functions of low-density lipoprotein receptor-related
protein 1 (LRP1). LRP1 is a multifunctional transmembrane protein involved in receptor-mediated endocytosis
and signal transduction. Since it binds to several molecules closely linked to AD development, LRP1 is
considered as a key molecule in the pathogenesis of AD. Previous reports suggested that LRP1 is involved in
the lipid and glucose metabolism, Aβ clearance, and propagation of phosphorylated tau between neurons.
However, there is still no consensus about the role of LRP1 in AD pathogenesis. To address this unsolved
problem, it is critical to accumulate knowledge about the functions of LRP1 in the normal brain. Through the
experiments supported by the parent active R01 award, we have found that LRP1 is highly expressed by
projection neurons, mitral and tufted cells, in the developing mouse OB, suggesting that LRP1 is involved in the
development of OB projection neurons. We also have found that the non-presynaptic bead-like axonal swellings
form along the mouse lateral olfactory tract (LOT), the bundle of mitral and tufted cell axons, and these swellings
contain a mitochondrial protein and an autophagy receptor. Interestingly, the number and size of the swellings
were increased in the LOT in an age-dependent manner. These findings suggest that the cellular metabolism of
OB projection neurons differs between the aged and young mice. Given that LRP1 plays a critical role in cellular
homeostasis, LRP1 may regulate the formation of axonal swellings in the LOT. As a first step to reveal the LRP1
function in the OB, we will examine whether LRP1 regulates the development and/or axonal swelling formation
of OB projection neurons. We will address this research goal by pursuing the following two specific aims. Specific
Aim 1 will determine the LRP1 expression pattern in the mouse OB at different ages from postnatal day 0 to 18
months old. Specific Aim 2 will examine the effects of LRP1 loss in the development and axonal swelling
formation of OB projection neurons. The results will reveal the roles of LRP1 in the development of OB projection
neurons and will provide us with significant insights into the LRP1 function in neuronal homeostasis. In this
regard, the proposed subproject will advance our knowledge about the molecular mechanisms regulating the
development of OB projection neurons and is an excellent pilot study to understand the contribution of LRP1 to
AD pathogenesis and age-related olfactor...

## Key facts

- **NIH application ID:** 10286220
- **Project number:** 3R01DC016307-04S1
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** Fumiaki Imamura
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $408,829
- **Award type:** 3
- **Project period:** 2017-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10286220

## Citation

> US National Institutes of Health, RePORTER application 10286220, Heterogeneity of mitral cell properties determined by the timing of neurogenesis - Supplement (3R01DC016307-04S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10286220. Licensed CC0.

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