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P1–046: Alterations of neurotrophin signaling in the retina of the P301S mutant human tau transgenic mouse
Author(s) -
Barini Erica,
Mazzaro Nadia,
Spillantini Maria Grazia,
Goedert Michel,
Medini Paolo,
Gasparini Laura
Publication year - 2013
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2013.05.266
Subject(s) - tropomyosin receptor kinase b , neurotrophin , tau protein , biology , retina , microbiology and biotechnology , neuroscience , tropomyosin receptor kinase a , neurotrophic factors , receptor , alzheimer's disease , pathology , medicine , genetics , disease
been reported in degenerative diseases of the retina. For instance, altered levels of tau protein have been detected in the retina and optic nerve of patients with glaucoma, suggesting that retina and brain degeneration share similar pathogenic mechanisms. We have recently demonstrated that P301S mutant human tau mice (tau P301S) develop tau filamentous inclusions and axonopathy in retinal ganglion neurons (RGCs), in the absence of neuronal loss and that transgenic retinal explants do not respond to neurotrophic stimuli in vitro. Methods:We investigated the impact of tau pathology on BDNF signaling pathway in RGC of adult wild type (WT) and tau P301S mice. Protein and mRNA expression of neurotrophins and their receptors was investigated by western blot and quantitative RT-PCR analyses in retina extracts of WT and tau P301S mice. The activation of the BDNF signaling pathway in vivo was evaluated under basal conditions and upon stimulation with the ligand. Results: Protein levels of BDNF and TrkB receptor were significantly altered in the retina of 5-month old tau P301S mice. The change was not due to altered expression and protein synthesis as the levels of mRNA and pro-BDNF were similar in WT and transgenic retinas. The activation of TrkB signaling was evaluated using antibodies directed towards specific phospho-tyrosine residues. Altered activation state was detected both in basal and BDNF-stimulated retinas of tau P301S mice. Conclusions: These data indicate that the presence of tau pathology is associated with alteration of neurotrophin signaling in the retina of tau P301S mice.