Pathological tau and reactive astrogliosis are associated with distinct functional deficits in a mouse model of tauopathy
| Autor: | Xavier Taylor, Abigail Perkins, Nur Jury, Cristian A. Lasagna-Reeves, Henika Patel, Pablo Martinez, David L. McKinzie |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
Male
Aging Mice Transgenic tau Proteins Disease Motor Activity Biology Protein Aggregation Pathological Article Grip strength medicine Animals Humans Gliosis Pathological Neuroinflammation Behavior Animal Frailty Hand Strength General Neuroscience medicine.disease Astrogliosis Disease Models Animal medicine.anatomical_structure Tauopathies Neuroinflammatory Diseases Female Neurology (clinical) Tauopathy Geriatrics and Gerontology medicine.symptom Neuroscience Body Temperature Regulation Developmental Biology Astrocyte |
| Zdroj: | Neurobiol Aging |
| ISSN: | 0197-4580 |
| DOI: | 10.1016/j.neurobiolaging.2021.09.006 |
| Popis: | Pathological aggregation of tau and neuroinflammatory changes mark the clinical course of Alzheimer's disease and related tauopathies. To understand the correlation between these pathological hallmarks and functional deficits, we assessed behavioral and physiological deficits in the PS19 mouse model, a broadly utilized model of tauopathy. At 9 months, PS19 mice have characteristic hyperactive behavior, a decline in motor strength, and deterioration in physiological conditions marked by lower body temperature, reduced body weight, and an increase in measures of frailty. Correlation of these deficits with different pathological hallmarks revealed that pathological tau species, characterized by soluble p-tau species, and tau seeding bioactivity correlated with impairment in grip strength and thermal regulation. On the other hand, astrocyte reactivity showed a positive correlation with the hyperactive behavior of the PS19 mice. These results suggest that a diverse spectrum of soluble pathological tau species could be responsible for different symptoms and that neuroinflammation could contribute to functional deficits independently from tau pathology. These observations enhance the necessity of a multi-targeted approach for the treatment of neurodegenerative tauopathies. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect