# Abnormal behaviors and glial responses in an animal model of tau pathology

## TL;DR

This study explores how glial cell responses in mice with tau pathology are linked to abnormal behaviors, shedding light on the role of neuroinflammation in neurodegenerative diseases.

## Contribution

The study identifies specific glial gene expressions associated with behavioral impairments in a tauopathy mouse model.

## Key findings

- rTg4510 mice showed impaired nest-building and exploratory behaviors compared to controls.
- Glial gene expressions in the prefrontal cortex correlated with behavioral abnormalities in these mice.
- Both 4- and 6-month-old rTg4510 mice exhibited increased time in open arms of the plus-maze test.

## Abstract

Tau hyperphosphorylation has been considered a major contributor to neurodegeneration in Alzheimer’s disease (AD) and frontotemporal dementia, and related tauopathies have gained prominence in the development of therapies for these conditions. Glial responses are key features of AD and frontotemporal dementia, and are associated with neuroinflammation. Numerous transgenic mouse models that recapitulate critical AD-like pathology and cognitive impairment have been developed to examine pathogenic mechanisms and evaluate therapeutic approaches targeting tau and glial reactivity. Glial reactivity and neuroinflammation coincide with tau hyperphosphorylation, which induces behavioral impairment; however, the specific correlation between glial cell activation and abnormal behavior remains unknown. In this study, we investigated changes in glial cell gene expressions related to abnormal behaviors in rTg4510 mice, which phenocopy the tau pathology, neuroinflammation, and neurodegeneration observed in human tauopathies. Both 4- and 6-month-old rTg4510 mice displayed significantly impaired nest-building behavior compared with control mice. Paired association learning was also impaired in 4-month-old rTg4510 mice. Moreover, rTg4510 mice of both age groups exhibited abnormal exploratory behavior, and these mice spent a longer time in the open arms of the plus-maze test than control mice. Using a magnetic-activated cell-sorting technique, we analyzed glial cell gene expressions related to neuroinflammation, phagocytosis, and amyloid synthesis in the prefrontal cortex of rTg4510 mice. Regression analysis of glial gene expressions and behavioral tests revealed that various glial reactivities were associated with behavioral abnormalities. Our findings suggest specific genetic characteristics of glial cells that may lead to abnormal behavior in rTg4510 mice.

The online version contains supplementary material available at 10.1186/s13041-025-01252-4.