Neuroprotective role of delta opioid receptors in hypoxic preconditioning

Şevin Güney,Gülnur Take-Kaplanoğlu,Sibel Di̇nçer,Güleser Göktaş

doi:10.3906/sag-1810-51

Abstract

Background/aimThe purpose of the present study was to explore the neuroprotective role of delta opioid receptors (DOR) in the rat cortex in hypoxic preconditioning.Materials and methodsRats were randomly divided into 8 groups: control (C), sham (S), hypoxic preconditioning (PC), severe hypoxia (SH), PC + SH, PC + SH + Saline (PS), PC + SH + DPDPE (DPDPE, selective DOR agonist), PC + SH + NT (NT, Naltrindole, selective DOR antagonist). Drugs were administered intracerebroventrically. Twenty four h after the end of 3 consecutive days of PC (10% O2, 2 h/day), the rats were subjected to severe hypoxia (7% O2 for 3 h). Bcl-2 and cyt-c were measured by western blot, and caspase-3 was observed immunohistochemically.ResultsBcl-2 expressions in the PC group were higher than in control, SH, and PC + SH groups. Even though there were no significant differences between the groups in terms of cyt-c levels, caspase-3 immunoreactivity of cortical neurons and glial cells in the severe hypoxia and NT groups were higher than in the control, sham, and hypoxic preconditioning groups. DPDPE administration diminished caspase-3 immunoreactivity compared with all of the severe hypoxia groups.ConclusionsThese results suggest that cortical cells are resistant to apoptosis via increased expression of Bcl-2 and decreased immunoreactivity of caspase-3 in the cortex, and that DOR is involved in neuroprotection induced by hypoxic preconditioning via the caspase-3 pathway in cortical neurons.

Highlights

Hypoxia can occur due to natural causes, such as travel to or living in high altitudes, or it can occur because of pathological events such as ischemia, cardiac arrest, or blood loss
Even though there were no significant differences between the groups in terms of cyt-c levels, caspase-3 immunoreactivity of cortical neurons and glial cells in the severe hypoxia and NT groups were higher than in the control, sham, and hypoxic preconditioning groups
DPDPE administration diminished caspase-3 immunoreactivity compared with all of the severe hypoxia groups. These results suggest that cortical cells are resistant to apoptosis via increased expression of Bcl-2 and decreased immunoreactivity of caspase-3 in the cortex, and that delta opioid receptors (DOR) is involved in neuroprotection induced by hypoxic preconditioning via the caspase-3 pathway in cortical neurons

Summary

Introduction

Hypoxia can occur due to natural causes, such as travel to or living in high altitudes, or it can occur because of pathological events such as ischemia, cardiac arrest, or blood loss. Hypoxia/ischemia triggers a variety of processes that lead to changes in intracellular signal transduction, membrane function, metabolism, and even cell morphology [1,2]. These processes may cause cellular damage or death. Hypoxic or ischemic preconditioning (PC or IPC) is based on a phenomenon in which transient and mild hypoxia/ischemia set cells and increase cellular resistance against subsequent lethal ischemic/hypoxic injury. Several studies have shown the protective effects of PC/IPC on different organs such as the kidney, lung, and heart in both in vivo and in vitro experimental

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