Format

Send to

Choose Destination
Neurobiol Dis. 2019 Jul;127:323-338. doi: 10.1016/j.nbd.2019.03.018. Epub 2019 Mar 21.

Neuropathological changes and cognitive deficits in rats transgenic for human mutant tau recapitulate human tauopathy.

Author information

1
Department of Anatomy and Cell Biology, McGill University, Montréal, QC H3A 0C7, Canada.
2
Department of Pharmacology and Therapeutics, McGill University, Montréal, QC H3G 1Y6, Canada.
3
Department of Neurology and Neurosurgery, McGill University, Montréal, QC H3A 2B4, Canada.
4
Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
5
Department of Anatomy and Cell Biology, McGill University, Montréal, QC H3A 0C7, Canada; Department of Pharmacology and Therapeutics, McGill University, Montréal, QC H3G 1Y6, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, QC H3A 2B4, Canada. Electronic address: claudio.cuello@mcgill.ca.

Abstract

The assembly of tau protein into abnormal filaments and brain cell degeneration are characteristic of a number of human neurodegenerative diseases, including Alzheimer's disease and frontotemporal dementia and parkinsonism linked to chromosome 17. Several murine models have been generated to better understand the mechanisms contributing to tau assembly and neurodegeneration. Taking advantage of the more elaborate central nervous system and higher cognitive abilities of the rat, we generated a model expressing the longest human tau isoform (2N4R) with the P301S mutation. This transgenic rat line, R962-hTau, exhibits the main features of human tauopathies, such as: age-dependent increase in inclusions comprised of aggregated-tau, neuronal loss, global neurodegeneration as reflected by brain atrophy and ventricular dilation, alterations in astrocytic and microglial morphology, and myelin loss. In addition, substantial deficits across multiple memory and learning paradigms, including novel object recognition, fear conditioning and Morris water maze tasks, were observed at the time of advanced tauopathy. These results support the concept that progressive tauopathy correlates with brain atrophy and cognitive impairment.

KEYWORDS:

Alzheimer's disease; FTDP-17T; Gliosis; Inflammation; Neurodegeneration; Neuronal loss; Rat model; Tauopathy

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center