Bergmeister 2022 Abstract Bioblast

P11. Bergmeister Lisa, Doerrier C, Gnaiger E, Schwarzer C (2022) The role of enkephalin in hypoxic preconditioning. Bioblast 2022: BEC Inaugural Conference. In: https://doi.org/10.26124/bec:2022-0001

Link: Bioblast 2022: BEC Inaugural Conference

Bergmeister Lisa, Doerrier Carolina, Gnaiger Erich, Schwarzer Christoph (2022)

Event: Bioblast 2022

Hypoxic preconditioning (HPC) is the application of mild transient hypoxia which protects the brain against a following more severe hypoxic insult as it occurs during epileptic seizures. HPC decreases seizure susceptibility and severity as well as neuronal damage in the hippocampus. The delta opioid receptor (DOR) and its primary endogenous ligands, the neuropeptides met- and leu-enkephalin (Enk), are thought to be involved in the neuroprotective actions of HPC. Recently, we showed that Enk influences mitochondrial respiration that may contribute to the neuroprotective effects of the Enk/DOR system. The present study aims at investigating the effects of the Enk/DOR system on structural and functional alterations of mitochondria in HPC.

Wild type (WT) and met-Enk-knockout (met-Enk-KO) mice were exposed to hypoxia. Subsequently, we determined the seizure threshold, analyzed mitochondrial function and dynamics.

In WT mice after HPC we observed an elevated seizure threshold, improved mitochondrial reserve capacity and increased mitochondrial fusion. In addition, our results suggest mitochondrial biogenesis after HPC in WT mice. Naïve met-Enk-KO mice had an increased seizure threshold and increased mitochondrial fusion but no changes upon HPC.

The observed mitochondrial alterations after HPC in WT mice could explain improved neuronal survival and increased seizure threshold. Enhanced mitochondrial reserve capacity improves energy supply in stress situations and increased mitochondrial fusion is associated with neuronal survival and elevated Ca²⁺ storage capacities. However, the precise role of met-Enk in HPC is unclear but we observed adaptive mechanisms in WT mice upon hypoxia which are absent in met-Enk-KO mice.

• Keywords: Hypoxic preconditioning, Enkephalin/delta opioid receptor system, Mitochondria, Epilepsy

• O2k-Network Lab: AT Innsbruck Oroboros

Affiliations and support

Bergmeister L¹, Doerrier C², Gnaiger², Schwarzer C¹

Department of Pharmacology, Medical University of Innsbruck, Innsbruck, Austria
Oroboros Instruments GmbH, Innsbruck, Austria

This study is supported by the Austrian Science Fund FWF (SPIN W-1206) and Oroboros Instruments GmbH.

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Labels: MiParea: Respiration, Genetic knockout;overexpression Pathology: Other Stress:Hypoxia Organism: Mouse

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