Reduced Axonal Transport and Increased Excitotoxic Retinal Ganglion Cell Degeneration in Mice Transgenic for Human Mutant P301S Tau

被引：49

作者：

Bull, Natalie D. ^{[1
]}

Guidi, Alessandra ^{[1
]}

Goedert, Michel ^{[4
]}

Martin, Keith R. ^{[1
,2
,3
]}

Spillantini, Maria Grazia ^{[1
]}

机构：

[1] Univ Cambridge, Dept Clin Neurosci, Cambridge Ctr Brain Repair, Cambridge, England

[2] Univ Cambridge, Dept Ophthalmol, Cambridge, England

[3] Univ Cambridge, Biomed Res Ctr, Cambridge Natl Inst Hlth Res, Cambridge, England

[4] Med Res Council Lab Mol Biol, Cambridge, England

来源：

PLOS ONE | 2012年 / 7卷 / 04期

基金：

英国医学研究理事会;

关键词：

FRONTOTEMPORAL DEMENTIA; NEUROTROPHIC FACTOR; MOUSE MODEL; PROTEIN; PHOSPHORYLATION; TAUOPATHY; FTDP-17; MUTATIONS; GLAUCOMA; BRAIN;

D O I：

10.1371/journal.pone.0034724

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：8

共 46 条

[1] Tau inclusions in retinal ganglion cells of human P301S tau transgenic mice: Effects on axonal viability [J].

Gasparini, Laura ;

Crowther, R. Anthony ;

Martin, Keith R. ;

Berg, Nicola ;

Coleman, Michael ;

Goedert, Michel ;

Spillantini, Maria Grazia .

NEUROBIOLOGY OF AGING, 2011, 32 (03) :419-433

[2] Early-onset cognitive deficits and axonal transport dysfunction in P301S mutant tau transgenic mice [J].

Onishi, Tomohiro ;

Matsumoto, Yoshio ;

Hattori, Masahiko ;

Obayashi, Yuka ;

Nakamura, Kimie ;

Yano, Takashi ;

Horiguchi, Takashi ;

Iwashita, Hiroki .

NEUROSCIENCE RESEARCH, 2014, 80 :76-85

[3] Progressive Motor Deficit is Mediated by the Denervation of Neuromuscular Junctions and Axonal Degeneration in Transgenic Mice Expressing Mutant (P301S) Tau Protein [J].

Yin, Zhuoran ;

Valkenburg, Femke ;

Hornix, Betty E. ;

Mantingh-Otter, Ietje ;

Zhou, Xingdong ;

Mari, Muriel ;

Reggiori, Fulvio ;

Van Dam, Debby ;

Eggen, Bart J. L. ;

De Deyn, Peter P. ;

Boddeke, Erik .

JOURNAL OF ALZHEIMERS DISEASE, 2017, 60 :S41-S57

[4] Contribution of endogenous antibodies to learning deficits and astrocytosis in human P301S mutant tau transgenic mice [J].

van der Hoven, Julia ;

van Hummel, Annika ;

Przybyla, Magdalena ;

Asih, Prita R. ;

Gajwani, Mehul ;

Feiten, Astrid F. ;

Ke, Yazi D. ;

Ittner, Arne ;

van Eersel, Janet ;

Ittner, Lars M. .

SCIENTIFIC REPORTS, 2020, 10 (01)

[5] Cryo-EM structures of tau filaments from the brains of mice transgenic for human mutant P301S Tau [J].

Schweighauser, Manuel ;

Murzin, Alexey G. ;

Macdonald, Jennifer ;

Lavenir, Isabelle ;

Crowther, R. Anthony ;

Scheres, Sjors H. W. ;

Goedert, Michel .

ACTA NEUROPATHOLOGICA COMMUNICATIONS, 2023, 11 (01)

[6] Rapamycin Attenuates the Progression of Tau Pathology in P301S Tau Transgenic Mice [J].

Ozcelik, Sefika ;

Fraser, Graham ;

Castets, Perrine ;

Schaeffer, Veronique ;

Skachokova, Zhiva ;

Breu, Karin ;

Clavaguera, Florence ;

Sinnreich, Michael ;

Kappos, Ludwig ;

Goedert, Michel ;

Tolnay, Markus ;

Winkler, David Theo .

PLOS ONE, 2013, 8 (05)

[7] Tauopathy-induced retinal dysfunction in the P301S mutant human tau transgenic mouse [J].

Nadia Mazzaro ;

Erica Barini ;

Michel Goedert ;

Maria Grazia Spillantini ;

Paolo Medini ;

Laura Gasparini .

Molecular Neurodegeneration, 8 (Suppl 1)

[8] Novel Behavioural Characteristics of Male Human P301S Mutant Tau Transgenic Mice - A Model for Tauopathy [J].

Watt, Georgia ;

Przybyla, Magdalena ;

Zak, Valeria ;

van Eersel, Janet ;

Ittner, Arne ;

Ittner, Lars M. ;

Karl, Tim .

NEUROSCIENCE, 2020, 431 :166-175

[9] Early behavioural markers of disease in P301S tau transgenic mice [J].

Scattoni, Maria Luisa ;

Gasparini, Laura ;

Alleva, Enrico ;

Goedert, Michel ;

Calamandrei, Gemma ;

Spillantini, Maria Grazia .

BEHAVIOURAL BRAIN RESEARCH, 2010, 208 (01) :250-257

[10] Memory deficits correlate with tau and spine pathology in P301S MAPT transgenic mice [J].

Xu, H. ;

Roesler, T. W. ;

Carlsson, T. ;

de Andrade, A. ;

Bruch, J. ;

Hoellerhage, M. ;

Oertel, W. H. ;

Hoeglinger, G. U. .

NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, 2014, 40 (07) :833-843

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