TrpV1 receptor activation rescues neuronal function and network gamma oscillations from Aβ-induced impairment in mouse hippocampus in vitro
- Karolinska Institute, Sweden
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
Hugo Balleza-Tapia
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.
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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TrpV1 receptor activation rescues neuronal function and network gamma oscillations from Aβ-induced impairment in mouse hippocampus in vitro
eLife 7:e37703.
https://doi.org/10.7554/eLife.37703
