Severe amygdala dysfunction in a MAPT transgenic mouse model of frontotemporal dementia |
| |
Authors: | Casey Cook Judy H. Dunmore Melissa E. Murray Kristyn Scheffel Nawsheen Shukoor Jimei Tong Monica Castanedes-Casey Virginia Phillips Linda Rousseau Michael S. Penuliar Aishe Kurti Dennis W. Dickson Leonard Petrucelli John D. Fryer |
| |
Affiliation: | 1. Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, FL, USA;2. Neurobiology of Disease Program, Mayo Graduate School, Rochester, MN, USA |
| |
Abstract: | Frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) is a neurodegenerative tauopathy caused by mutations in the tau gene (MAPT). Individuals with FTDP-17 have deficits in learning, memory, and language, in addition to personality and behavioral changes that are often characterized by a lack of social inhibition. Several transgenic mouse models expressing tau mutations have been tested extensively for memory or motor impairments, though reports of amygdala-dependent behaviors are lacking. To this end, we tested the rTg4510 mouse model on a behavioral battery that included amygdala-dependent tasks of exploration. As expected, rTg4510 mice exhibit profound impairments in hippocampal-dependent learning and memory tests, including contextual fear conditioning. However, rTg4510 mice also display an abnormal hyperexploratory phenotype in the open-field assay, elevated plus maze, light-dark exploration, and cued fear conditioning, indicative of amygdala dysfunction. Furthermore, significant tau burden is detected in the amygdala of both rTg4510 mice and human FTDP-17 patients, suggesting that the rTg4510 mouse model recapitulates the behavioral disturbances and neurodegeneration of the amygdala characteristic of FTDP-17. |
| |
Keywords: | Frontotemporal dementia Tau Tauopathy Amygdala Neurodegeneration |
本文献已被 ScienceDirect 等数据库收录! |
|