Abstract
Background: It is controversially discussed whether general anaesthesia increases the risk of Alzheimer's disease (AD) or accelerates its progression. One important factor in AD pathogenesis is the accumulation of soluble amyloid beta (Aβ) oligomers which affect N-methyl-D-aspartate (NMDA) receptor function and abolish hippocampal long-term potentiation (LTP). NMDA receptor antagonists, at concentrations allowing physiological activation, can prevent Aβ-induced deficits in LTP. The anaesthetics xenon and S-ketamine both act as NMDA receptor antagonists and have been reported to be neuroprotective. In this study, we investigated the effects of subanaesthetic concentrations of these drugs on LTP deficits induced by different Aβ oligomers and compared them to the effects of radiprodil, a NMDA subunit 2B (GluN2B)-selective antagonist. Methods: We applied different Aβ oligomers to murine brain slices and recorded excitatory postsynaptic field potentials before and after high-frequency stimulation in the CA1 region of hippocampus. Radiprodil, xenon and S-ketamine were added and recordings evoked from a second input were measured. Results: Xenon and radiprodil, applied at low concentrations, partially restored the LTP deficit induced by pre-incubated Aβ 1-42 . S-ketamine showed no effect. None of the drugs tested were able to ameliorate Aβ 1-40 -induced LTP-deficits. Conclusions: Xenon administered at subanaesthetic concentrations partially restored Aβ 1-42 -induced impairment of LTP, presumably via its weak NMDA receptor antagonism. The effects were in a similar range than those obtained with the NMDA-GluN2B antagonist radiprodil. Our results point to protective properties of xenon in the context of pathological distorted synaptic physiology which might be a meaningful alternative for anaesthesia in AD patients.
Original language | English |
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Pages (from-to) | 21-32 |
Number of pages | 12 |
Journal | Neuropharmacology |
Volume | 151 |
DOIs | |
State | Published - Jun 2019 |
Keywords
- Alzheimer's disease
- Amyloid beta (Aβ)
- Anaesthesia
- Ketamine
- Long-term potentiation (LTP)
- Xenon