Restoration of sFRP3 Preserves the Neural Stem Cell Pool and Spatial Discrimination Ability in a Mouse Model of Alzheimer's Disease

Authors

• Chia-Hsuan Fu
• Jin Park
• Umberto Tosi
• Francisco A Blanco
• Manuel Silva-Pérez
• Kavitha Muralidharan
• Jason C You
• Minjung Lee
• Gabriel S Stephens
• Xiaohong Zhang
• Yi Zheng
• Helen Scharfman
• Kimberley F Tolias
• Jeannie Chin

Language

English

Publication Date

12-3-2025

Journal

Journal of Neuroscience

DOI

10.1523/JNEUROSCI.0049-25.2025

PMID

41136336

PMCID

PMC12677132

PubMedCentral® Posted Date

10-24-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Individuals with Alzheimer's disease (AD) have an increased incidence of seizures, which worsen cognitive decline. Using a transgenic mouse model of AD neuropathology that exhibits spontaneous seizures, we previously found that seizure activity stimulates and accelerates depletion of the hippocampal neural stem cell (NSC) pool, which was associated with deficits in neurogenesis-dependent spatial discrimination. However, the precise molecular mechanisms that drive seizure-induced activation and depletion of NSCs are unclear. Here, using mice of both sexes, we performed RNA-sequencing on the hippocampal dentate gyrus and identified differentially expressed regulators of neurogenesis in the Wnt signaling pathway that regulates many aspects of cell proliferation. We found that the expression of sFRP3, a Wnt signaling inhibitor, is altered in a seizure-dependent manner and might be regulated by ΔFosB, a seizure-induced transcription factor. Increasing sFRP3 expression prevented NSC depletion and improved spatial discrimination, suggesting that the loss of sFRP3 might mediate seizure-driven impairment in cognition in AD model mice and perhaps also in AD.

Keywords

Animals, Alzheimer Disease, Mice, Neural Stem Cells, Male, Mice, Transgenic, Female, Disease Models, Animal, Neurogenesis, Mice, Inbred C57BL, Dentate Gyrus, Wnt Signaling Pathway, Seizures, Intracellular Signaling Peptides and Proteins, Hippocampus, adult hippocampal neurogenesis, adult neural stem cells, Alzheimer's disease, dentate gyrus, epilepsy, seizures

Published Open-Access

yes

Recommended Citation

Fu, Chia-Hsuan; Park, Jin; Tosi, Umberto; et al., "Restoration of sFRP3 Preserves the Neural Stem Cell Pool and Spatial Discrimination Ability in a Mouse Model of Alzheimer's Disease" (2025). Faculty, Staff and Students Publications. 7241.
https://digitalcommons.library.tmc.edu/baylor_docs/7241