Reduced axonal transport and increased excitotoxic retinal ganglion cell degeneration in mice transgenic for human mutant P301S tau

The effects of tau hyperphosphorylation and aggregation on axonal transport were investigated in the optic nerve of mice transgenic for human mutant P301S tau. Transport was examined using cholera toxin B tracing. Retrograde transport was reduced in transgenic mice at 3 and 5 months of age, when com...

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Bibliographic Details
Published in:PloS one 2012-04, Vol.7 (4), p.e34724
Main Authors: Bull, Natalie D, Guidi, Alessandra, Goedert, Michel, Martin, Keith R, Spillantini, Maria Grazia
Format: Article
Language:English
Subjects:
Age
Agglomeration
Animals
Axonal Transport
Biology
Brain research
Brain-derived neurotrophic factor
Cholera
Cholera toxin
Cholera Toxin - metabolism
Cholera toxin B subunit
Comparative analysis
Degeneration
Dementia
Ethics
Excitotoxicity
Ganglion cysts
Genetic engineering
Glaucoma
Humans
Infections
Injury prevention
Laboratory animals
Male
Medicine
Mice
Mice, Inbred C57BL
Mice, Transgenic
Mutation
Neurodegeneration
Neurodegenerative diseases
Neurons
Neuroprotection
Neurosciences
Optic nerve
Phosphorylation
Physiological aspects
Proteins
Public health
Retina
Retinal Degeneration - metabolism
Retinal Degeneration - pathology
Retinal ganglion cells
Retinal Ganglion Cells - metabolism
Retinal Ganglion Cells - pathology
Retrograde transport
Rodents
Spinal cord
Tau protein
tau Proteins - genetics
tau Proteins - metabolism
Tauopathies - metabolism
Tauopathies - pathology
Transgenic animals
Transgenic mice
Transport
Waterborne diseases
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Summary:The effects of tau hyperphosphorylation and aggregation on axonal transport were investigated in the optic nerve of mice transgenic for human mutant P301S tau. Transport was examined using cholera toxin B tracing. Retrograde transport was reduced in transgenic mice at 3 and 5 months of age, when compared to C57/Bl6 control mice. Anterograde axonal transport was also reduced in 3-month-old transgenic mice. Mild excitotoxic injury of retinal ganglion cells resulted in greater nerve cell loss in retinas from 3- and 5-month old P301S transgenic mice, when compared to controls. In conjunction with the detection of abnormal tau in the optic nerve in human and experimental glaucoma, the present findings suggest that tau hyperphosphorylation and aggregation may constitute targets for neuroprotective therapies in glaucoma as well as tauopathies.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0034724