Targeting Astrogliosis in the Retrotrapezoid Nucleus: A Novel Approach to Ameliorate Respiratory Dysfunction and Alzheimer's Pathology in Mice

Authors

Zahid Iqbal
Ahmad El Hamamy
Ngoc Mai Le
Arya Ranjan
YuXing Zhang
Li Qi
Bharti Manwani
Chunfeng Tan
Louise D McCullough
Jun Li

Language

English

Publication Date

7-26-2024

Journal

Aging and Disease

DOI

10.14336/AD.2024.0523

PMID

39812538

PMCID

PMC12221388

PubMedCentral® Posted Date

7-26-2024

PubMedCentral® Full Text Version

Post-print

Abstract

Alzheimer's disease (AD), a leading cause of dementia, is associated with significant respiratory dysfunctions. Our study explores the role of astrogliosis in the brainstem retrotrapezoid nucleus (RTN), a key breathing regulatory center, and its impact on breathing control and AD pathology in mice. Using Tg-2576 AD and wild-type mice, we investigated the effect of silencing the transforming growth factor-beta receptor II (TGFβR II) in the RTN. We performed behavioral tests, including the Barnes maze and novel object recognition test, along with whole-body plethysmography to assess breathing disorders. Our results showed that AD mice exhibited increased apneas and cognitive impairment, which were significantly mitigated following TGFβR II gene silencing. Immunohistochemistry revealed elevated levels of GFAP and TGFβR II in the RTN of AD mice, which were reduced post-gene silencing, alongside a decrease in amyloid-beta expression in the cortex and hippocampus. These findings suggest that targeting astrogliosis and improving respiratory control may offer a novel therapeutic avenue for managing Alzheimer's disease. Our study provides the first mechanistic insights into how TGFβ signaling influences both respiratory control and AD pathogenesis, highlighting the potential benefits of stabilizing breathing patterns in AD treatment.

Keywords

Animals, Alzheimer Disease, Gliosis, Mice, Mice, Transgenic, Disease Models, Animal, Receptor, Transforming Growth Factor-beta Type II, Male, Amyloid beta-Peptides, Astrocytes, Respiration Disorders, Alzheimer's disease, Disordered breathing, TGFβR II, RTN

Published Open-Access

yes

Recommended Citation

Iqbal, Zahid; El Hamamy, Ahmad; Le, Ngoc Mai; et al., "Targeting Astrogliosis in the Retrotrapezoid Nucleus: A Novel Approach to Ameliorate Respiratory Dysfunction and Alzheimer's Pathology in Mice" (2024). Faculty, Staff and Student Publications. 6136.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6136