1. Neuroscience
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TrpV1 receptor activation rescues neuronal function and network gamma oscillations from Aβ-induced impairment in mouse hippocampus in vitro

Research Article
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Cite this article as: eLife 2018;7:e37703 doi: 10.7554/eLife.37703

Abstract

Amyloid-β peptide (Aβ) forms plaques in Alzheimer's Disease (AD) and is responsible for early cognitive deficits in AD patients. Advancing cognitive decline is accompanied by progressive impairment of cognition-relevant EEG patterns such as gamma oscillations. The endocannabinoid anandamide, a TrpV1-receptor agonist, reverses hippocampal damage and memory impairment in rodents and protects neurons from Aβ-induced cytotoxic effects. Here we investigate a restorative role of TrpV1-receptor activation against Aβ-induced degradation of hippocampal neuron function and gamma oscillations. We found that the TrpV1-receptor agonist capsaicin rescues Aβ-induced degradation of hippocampal gamma oscillations by reversing both the desynchronization of AP firing in CA3 pyramidal cells and the shift in excitatory/inhibitory current balance. This rescue effect is TrpV1-receptor-dependent since it was absent in TrpV1 knockout mice or in the presence of the TrpV1-receptor antagonist capsazepine. Our findings provide novel insight into the network mechanisms underlying cognitive decline in AD and suggest TrpV1 activation as a novel therapeutic target.

Data availability

Source data files have been provided for all figures, figure supplements, and the unitary action potential recordings.

Article and author information

Author details

  1. Hugo Balleza-Tapia

    Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institute, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3045-4594
  2. Sophie Crux

    Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institute, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  3. Yuniesky Andrade-Talavera

    Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institute, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  4. Pablo Dolz-Gaiton

    Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institute, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  5. Daniela Papadia

    Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institute, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  6. Gefei Chen

    Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institute, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  7. Jan Johansson

    Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institute, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  8. André Fisahn

    Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institute, Stockholm, Sweden
    For correspondence
    andre.fisahn@ki.se
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1480-175X

Funding

Vetenskapsrådet

  • André Fisahn

Alzheimerfonden

  • Jan Johansson

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Experiments were performed in accordance with the ethical permit granted by Norra Stockholms Djurförsöksetiska Nämnd to AF (N45/13). Animals used in this study included p17-30 C57BL/6 (WT) and TrpV1 knockout (TrpV1 KO) male mice (Charles River Laboratories and Jackson Laboratory, respectively). Animals were deeply anesthetized using isoflurane before being sacrificed by decapitation.

Reviewing Editor

  1. Michel Goedert, University of Cambridge, United Kingdom

Publication history

  1. Received: April 19, 2018
  2. Accepted: November 8, 2018
  3. Accepted Manuscript published: November 12, 2018 (version 1)
  4. Version of Record published: December 5, 2018 (version 2)

Copyright

© 2018, Balleza-Tapia et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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