Melatonin mitigates cisplatin-induced cognitive impairment in rats and improves hippocampal dendritic spine density

Author:

Qutifan Shahd1,Saleh Tareq2,Abu Shahin Nisreen3,ELBeltagy Maha14,Obeidat Fatimah3,Qattan Duaa3,Kalbouneh Heba1,Barakat Noor A.5,Alsalem Mohammad1

Affiliation:

1. Department of Anatomy and Histology, School of Medicine, The University of Jordan, Amman

2. Department of Pharmacology and Public Health, Faculty of Medicine, The Hashemite University, Zarqa

3. Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman, Jordan

4. Human Anatomy and Embryology, Faculty of Medicine, Menoufia University, Shibin El Kom, Egypt

5. Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Middle East University, Amman, Jordan

Abstract

Cisplatin-induced cognitive impairment (chemobrain) affects a considerable percentage of cancer patients and has no established pharmacological treatment. Chemobrain can be associated with neuroinflammation and oxidative stress. Melatonin, a pineal hormone, is known to have antioxidant, anti-inflammatory and neuroprotective potential. In this study, we investigated cisplatin-induced cognitive impairment in rats and whether melatonin can improve or reverse this impairment. Behavioral testing involved measuring working memory using the novel location recognition test (NLRT) under conditions of cisplatin or cisplatin + melatonin treatment, followed by the collection of rats’ brains. The brains were subsequently stained with Golgi-Cox stain and then the hippocampus area CA3 of each one was examined, and dendritic spine density was calculated. Treatment with cisplatin resulted in deficits in the rats’ performance in the NLRT (P < 0.05). These deficits were prevented by the coadministration of melatonin (P < 0.05). Cisplatin also reduced the density of dendritic spines in the hippocampus (P < 0.0001), specifically CA3 area, while the coadministration of melatonin significantly reversed this reduction (P < 0.001). This study showed that melatonin can ameliorate cisplatin-induced spatial memory deficits and dendritic spines density abnormalities in rats. Given that melatonin is a safe and wildly used supplement, it is feasible to explore its use as a palliative intervention in cancer treatment.

Publisher

Ovid Technologies (Wolters Kluwer Health)

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