Volume 8 Supplement 1

Molecular Neurodegeneration: Basic biology and disease pathways

Open Access

Tauopathy-induced retinal dysfunction in the P301S mutant human tau transgenic mouse

  • Nadia Mazzaro1,
  • Erica Barini1,
  • Michel Goedert2,
  • Maria Grazia Spillantini3,
  • Paolo Medini1 and
  • Laura Gasparini1
Molecular Neurodegeneration20138(Suppl 1):P57

https://doi.org/10.1186/1750-1326-8-S1-P57

Published: 4 October 2013

Intracellular inclusions made of microtubule-associated tau protein are a defining pathological hallmark of tauopathies, which include Alzheimer disease and familial frontotemporal dementia and parkinsonism linked to chromosome 17. Altered levels of tau protein have been detected in the retina and optic nerve of patients with glaucoma, suggesting that retina degeneration and tauopathies share similar pathogenic mechanisms. We have recently demonstrated that P301S mutant human tau (tauP301S) mice develop tau filamentous inclusions and axonopathy in retinal ganglion neurons (RGCs), in the absence of neuronal loss or alterations in the outer retina. Moreover, we showed that tauP301S transgenic retinal explants do not respond to neurotrophic stimuli in vitro. Here, we investigated the impact of tau pathology on RGC physiology in living animals and neurotrophin signaling pathways in vivo. In anesthetized 5-month old wild type (WT) and tauP301S mice, we measured RGCs activity using pattern electroretinogram (pERG), which selectively detects RGC response upon pattern light stimuli exposure. In transgenic tauP301S mice the amplitude of both P1 positive and N2 negative components of pERG at saturating contrast and spatial frequency was significantly smaller than WT values. Furthermore, retinal acuity was significantly reduced in tauP301S mice. Using uniform flickers of light (flash ERG), we measured the activity of the outer retina and found that outer retina response was preserved in tauP301S mice. Neurotrophins, and especially brain-derived neurotrophic factor (BDNF), are important modulators of neuronal survival and function in the brain and in the visual system. We therefore investigated the BDNF signaling pathway and found that BDNF signalling was altered in tauP301S transgenic retinas. Our results indicate that, in the tauP301S mouse, tau pathology specifically impairs the activity of RGCs, without affecting the outer retina function and is associated with BDNF signalling alterations. Given the role of BDNF in synaptic plasticity, these data suggest that mild levels of tau pathology are sufficient to trigger significant neuronal dysfunction possibly through alteration of neurotrophic signalling. Funded by a grant of Compagnia di San Paolo awarded to LG.

Authors’ Affiliations

(1)
Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia
(2)
MRC Laboratory of Molecular Biology
(3)
Cambridge Centre for Brain Repair, University of Cambridge

Copyright

© Mazzaro et al; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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