Journal Article

Structural abnormalities in the cortex of the rTg4510 mouse model of tauopathy: a light and electron microscopy study

Lewis, Jada, Ludvigson, Adam E., Peters, Alan, Luebke, Jennifer I.

2011

Overview

rTg4510 transgenic (TG) mice overexpress mutant (P301L) human tau protein. We have compared the dorsal premotor cortex of TG mice versus non-transgenic (NT) mice at 4, 9, and 13 months of age, using light (LM) and electron microscopy (EM). LM assessment shows that cortical thickness in TG mice is reduced by almost 50% from 4 to 13 months of age, while at the same time layer I thickness is reduced by 80%, with most of the cortical thinning occurring between 4 and 9 months. In TG mice, spherical, empty vacuoles, up to 60 μm in diameter, become increasingly abundant with age and by 9 months, pyramidal and non-pyramidal neurons with large intracellular tangles of tau protein are common throughout the cortex. These tangles occur in the perikarya; we have not observed them entering into cellular processes, nor have we observed ghost tangles in the intercellular matrix. In TG mice, nerve fiber pathology is widespread by 13 months, and split myelin sheaths, ballooned sheaths, and swollen axons containing mitochondrial aggregations are all common. Astrocytes become increasingly filled with glial filaments as TG mice age, and microglial cells almost always contain phagocytic inclusions. However, no glial cells are seen to contain tau in their cytoplasm. These observations add to the base of knowledge available on this commonly employed model of tauopathy.

• Publisher: Springer-Verlag,Springer Nature B.V
• Subject: Age / Aging / Animal models / Animals / Astrocytes / Astrocytes - metabolism / Astrocytes - ultrastructure / Axons / Axons - ultrastructure / Biomedical and Life Sciences / Biomedicine / Brain / Cell Biology / Cortex (premotor) / Cytoplasm / Disease Models, Animal / Electron microscopy / Fibers / Filaments / Functional anatomy / Humans / Mice / Mice, Transgenic / Microglial cells / Microscopy, Electron, Transmission / Mitochondria / Motor Cortex - metabolism / Motor Cortex - ultrastructure / Myelin / Myelin Sheath - metabolism / Myelin Sheath - ultrastructure / Nerve Fibers - metabolism / Nerve Fibers - ultrastructure / Neurodegenerative diseases / Neurology / Neurosciences / Original Article / Pathology / Pyramidal cells / Pyramidal Cells - metabolism / Pyramidal Cells - ultrastructure / Rodents / Structure-function relationships / Tau protein / tau Proteins - metabolism / Tauopathies - metabolism / Tauopathies - pathology / Thinning / Transgenic animals / Vacuoles / Vacuoles - metabolism / Vacuoles - ultrastructure