Near Infrared Light Treatment Reduces Synaptic Levels of Toxic Tau Oligomers in Two Transgenic Mouse Models of Human Tauopathies

Michele M. Comerota, Batbayar Tumurbaatar, Balaji Krishnan, Rakez Kayed, Giulio Taglialatela

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Tau oligomers are emerging as a key contributor to the synaptic dysfunction that drives cognitive decline associated with the clinical manifestation and progression of Alzheimer’s disease (AD). Accordingly, there is ample consensus that interventions that target tau oligomers may slow or halt the progression of AD. With this ultimate goal in mind, in the present study, we investigated tau oligomer accumulation and its synaptic and behavioral consequences after an in vivo treatment with near infrared (NIR) light (600–1000 nm) in two transgenic mouse models, overexpressing human tau either alone (hTau mice) or in combination with amyloid beta (3xTgAD mice). We found that a 4-week exposure to NIR light (90 s/day/5 days a week) significantly reduced levels of endogenous total and oligomeric tau in both synaptosomes and total protein extracts from the hippocampus and cortex of hTau mice and improved deteriorating memory function. Similar results were observed in the 3xTgAD mice, which further displayed reduced synaptic Aβ after NIR light treatment. On the other hand, ex vivo binding of tau oligomers in isolated synaptosomes as well as tau oligomer-induced depression of long-term potentiation (LTP) in hippocampal slices from NIR light-treated wt mice were unaffected. Finally, levels of proteins critically involved in two mechanisms associated with clearance of misfolded tau, inducible HSP70 and autophagy, were upregulated in NIR light treated mice. Collectively, these results show that NIR light decreases levels of endogenous toxic tau oligomers and alleviate associated memory deficits, thus furthering the development of NIR light as a possible therapeutic for AD.

Original languageEnglish (US)
Pages (from-to)3341-3355
Number of pages15
JournalMolecular Neurobiology
Volume56
Issue number5
DOIs
StatePublished - May 1 2019

Keywords

  • 3xTgAD mouse
  • Autophagy
  • Near infrared light
  • Tau oligomers
  • hTau mouse

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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