title: Reduced axonal transport and increased excitotoxic retinal ganglion cell degeneration in mice transgenic for human mutant P301S tau.
abstract: 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.
authors.affiliation: Cambridge Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom.
authors.forename: Natalie D
authors.initials: ND
authors.lastname: Bull
authors.forename: Alessandra
authors.initials: A
authors.lastname: Guidi
authors.forename: Michel
authors.initials: M
authors.lastname: Goedert
authors.forename: Keith R
authors.initials: KR
authors.lastname: Martin
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Spillantini
mesh_terms: D000818:Animals; D001370:Axonal Transport; D002772:Cholera Toxin / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D010766:Phosphorylation; D012162:Retinal Degeneration / Q000378:metabolism / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000378:metabolism* / Q000473:pathology; D024801:Tauopathies / Q000378:metabolism / Q000473:pathology; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins; D002772:Cholera Toxin