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Melatonin Improves Reduced Activities of Membrane ATPases and Preserves Ultrastructure of Gray and White Matter in the Rat Brain Ischemia/Reperfusion Model

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Abstract

Ischemia/reperfusion (I/R) is among the most frequent neurological problems and early intervention to limit the damage is crucial in decreasing mortality and morbidity. Based on reports regarding beneficial effects of melatonin, we investigated its impact on Na+-K+/Mg2+ ATPase and Ca2+/Mg2+ ATPase activities and ultrastructure of gray and white matter in the rat forebrain I/R model. Adult Wistar-albino rats (n = 78), were randomized into control, ischemia (I), ischemia/reperfusion (I/R), low (I/R + melatonin 400 µg/kg), moderate (I/R + melatonin 1200 µg/kg), and high (I/R + melatonin 2400 µg/kg) dose melatonin. Two-vessel occlusion combined with hypotension (15 min) induced ischemia and reperfusion (75 min) achieved by blood reinfusion were performed. Activities of the membrane-bound enzyme, brain malondialdehyde levels, and brain matter ultrastructure were examined in frontoparietal cortices. Melatonin lowered production of malondialdehyde in a dose-dependently. The enzyme activities attenuated under I and I/R, improved with melatonin treatment. I and I/R severely disturbed gray and white matter morphology. Melatonin, in all applied doses, decreased ultrastructural damages in both gray and white matter. Favorable effects of melatonin can be attributed to its antioxidant properties suggesting that it could be a promising neuroprotective agent against I/R injury being effective both for gray and white matter due to favorable biological properties.

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Abbreviations

EEG:

electroencephalography

I/R:

ischemia/reperfusion

MABP:

mean arterial blood pressure

MDA:

malondialdehyde

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Acknowledgments

The authors are grateful to Prof. Z. Dicle Balkancı, MD, Retired Professor of Physiology, for her critical contributions to the study and to Prof. A. Ergun Karaağaoğlu PhD, Professor of Biostatistics, for his involvement in statistical analysis.

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Authors and Affiliations

  1. Department of Physiology, Hacettepe University Faculty of Medicine, 06100, Ankara, Turkey

    Meltem Tuncer & Bilge Pehlivanoglu

  2. Department of Anatomy, Koç University School of Medicine, 34450, Istanbul, Turkey

    Selçuk H. Sürücü

  3. Department of Medical Biology, Faculty of Medicine, Yeditepe University, 34755, Istanbul, Turkey

    Turgay Isbir

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  1. Meltem Tuncer
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  2. Bilge Pehlivanoglu
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Meltem Tuncer and Bilge Pehlivanoğlu. Ultrastructural analysis was performed by Selçuk Sürücü and Biochemical measurements were carried out by Turgay İsbir. The first draft of the manuscript was written by Meltem Tuncer and Bilge Pehlivanoğlu; all authors commented on the previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Meltem Tuncer.

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The authors declare no conflict of interest in financial or any other sphere. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Tuncer, M., Pehlivanoglu, B., Sürücü, S.H. et al. Melatonin Improves Reduced Activities of Membrane ATPases and Preserves Ultrastructure of Gray and White Matter in the Rat Brain Ischemia/Reperfusion Model. Biochemistry Moscow 86, 540–550 (2021). https://doi.org/10.1134/S0006297921050035

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