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Gamma-patterned sensory stimulation reverses synaptic plasticity deficits in rat models of early Alzheimer's disease
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  • Yin Yang,
  • Tomas Ondrejcak,
  • Neng-Wei Hu,
  • Sadia Islam,
  • Eugene O'Rourke,
  • Richard Reilly,
  • Colm Cunningham,
  • Michael Rowan,
  • Igor Klyubin
Yin Yang
Trinity College Dublin
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Tomas Ondrejcak
Trinity College Dublin
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Neng-Wei Hu
Trinity College Dublin
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Sadia Islam
Trinity College Dublin
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Eugene O'Rourke
Trinity College Dublin
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Richard Reilly
Trinity College Dublin
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Colm Cunningham
Trinity College Dublin
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Michael Rowan
Trinity College Dublin
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Igor Klyubin
Trinity College Dublin

Corresponding Author:klyubini@tcd.ie

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Abstract

Non-invasive sensory stimulation in the range of the brain’s gamma rhythm (30-100 Hz) is emerging as a new potential therapeutic strategy for the treatment of Alzheimer’s disease (AD). Here we investigated the effect of repeated combined exposure to 40 Hz synchronized sound and light stimuli on hippocampal long-term potentiation (LTP) in vivo in three rat models of early AD. We employed a very complete model of AD amyloidosis, amyloid precursor protein (APP)-overexpressing transgenic McGill-R-Thy1-APP rats at an early pre-plaque stage, systemic treatment of transgenic APP rats with corticosterone modelling certain environmental AD risk factors and, importantly, intracerebral injection of highly disease-relevant AD patient-derived synaptotoxic beta-amyloid and tau in wild-type animals. We found that daily sessions of 40 Hz sensory stimulation fully abrogated the inhibition of LTP in all three models. Moreover, there was a negative correlation between the magnitude of LTP and the level of active caspase-1 in the hippocampus of transgenic APP animals which suggests that the beneficial effect of 40 Hz stimulation was dependent on modulation of pro-inflammatory mechanisms. Our findings support ongoing clinical trials of gamma-patterned sensory stimulation in early AD.
05 Feb 2023Submitted to European Journal of Neuroscience
06 Feb 2023Submission Checks Completed
06 Feb 2023Assigned to Editor
06 Feb 2023Review(s) Completed, Editorial Evaluation Pending
13 Feb 2023Reviewer(s) Assigned
21 May 2023Editorial Decision: Revise Major
29 Jun 20231st Revision Received
30 Jun 2023Submission Checks Completed
30 Jun 2023Assigned to Editor
30 Jun 2023Review(s) Completed, Editorial Evaluation Pending
26 Jul 2023Reviewer(s) Assigned
09 Aug 2023Editorial Decision: Accept