Melatonin alleviates asphyxial cardiac arrest-induced cerebellar Purkinje cell death by attenuation of oxidative stress.

Abstract

Although multiple reports using animal models have confirmed that melatonin appears to promote neuroprotective effects following ischemia/reperfusion-induced brain injury, the relationship between its protective effects and activation of autophagy in Purkinje cells following asphyxial cardiac arrest and cardiopulmonary resuscitation (CA/CPR) remains unclear. Rats used in this study were randomly assigned to 6 groups as follows; vehicle-treated sham operated group, vehicle-treated asphyxial CA/CPR operated group, melatonin-treated sham operated group, melatonin-treated asphyxial CA/CPR operated group, PDOT (a MT2 melatonin receptor antagonist) plus (+) melatonin-treated sham operated group and PDOT+melatonin-treated asphyxial CA/CPR operated group. Melatonin (20 mg/kg, i.p., 4 times before CA and 3 times after CA) treatment significantly improved survival rate and neurological deficit compared with the vehicle-treated asphyxial CA/CPR rats (survival rates ≥40% vs 10%), showing that melatonin treatment exhibited protective effect against asphyxial CA/CPR-induced Purkinje cell death. The protective effect of melatonin against CA/CPR-induced Purkinje cell death paralleled a remarkable attenuation of autophagy-like processes (Beclin-1, Atg7 and LC3), as well as a dramatic reduction in superoxide anion radical (O2·-), intense enhancements of CuZn superoxide dismutase (SOD1) and MnSOD (SOD2) expressions. Furthermore, the protective effect was notably reversed by treatment with PDOT, which is a selective MT2 antagonist. In brief, melatonin conferred neuroprotection against asphyxial CA/CPR-induced Purkinje cell death via inhibiting autophagic activation by reducing expressions of O2·- and increasing expressions of antioxidant enzymes, and suggests that MT2 is involved in neuroprotective effect of melatonin against Purkinje cell death caused by asphyxial CA/CPR.

• Authors: Jeong Hwi Cho, Hyun-Jin Tae, In-Shik Kim, Minah Song, Hyunjung Kim, Tae-Kyeong Lee, Young-Myeong Kim, Sungwoo Ryoo, Dae Won Kim, Choong-Hyun Lee, In Koo Hwang, Bing Chun Yan, Il Jun Kang, Moo-Ho Won, Jae-Chul Lee
• Journal: Experimental neurology (Exp Neurol) Vol. 320 Pg. 112983 (10 2019) ISSN: 1090-2430 [Electronic] United States
• PMID: 31251935 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Antioxidants
• Neuroprotective Agents
• Receptor, Melatonin, MT2
• Melatonin

Topics

• Animals
• Antioxidants (pharmacology)
• Asphyxia (etiology)
• Autophagy (drug effects)
• Heart Arrest (complications, pathology)
• Male
• Melatonin (pharmacology)
• Neuroprotective Agents (pharmacology)
• Oxidative Stress (drug effects)
• Purkinje Cells (drug effects, metabolism, pathology)
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Receptor, Melatonin, MT2 (metabolism)