Apiwat Sirichoat1, Kornrawee Suwannakot2, Pornthip Chaisawang3, Wanassanun Pannangrong2, Anusara Aranarochana2, Peter Wigmore4, Jariya Umka Welbat5. 1. Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; Neuroscience Research and Development Group, Khon Kaen University, Khon Kaen 40002, Thailand. 2. Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. 3. Faculty of Medical Science, Nakhonratchasima College, Nakhon Ratchasima 30000, Thailand. 4. School of Life Sciences, Medical School, Queen's Medical Centre, The University of Nottingham, Nottingham, United Kingdom. 5. Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; Neuroscience Research and Development Group, Khon Kaen University, Khon Kaen 40002, Thailand. Electronic address: jariya@kku.ac.th.
Abstract
AIMS: Treatment with 5-fluorouracil (5-FU) can cause impairment to adult hippocampal neurogenesis, resulting in cognitive deficits. As melatonin has been shown to enhance memory and hippocampal neurogenesis in animal models, this research investigated the neuroprotective effects of melatonin against spatial memory and hippocampal neurogenesis impairment in 5-fluorouracil (5-FU)-treated rats. MATERIALS AND METHODS: Four-Five weeks old male Spraque-Dawley rats weighing between 180 and 200 g were used. Animals were maintained under standard laboratory conditions with 25 °C and 12 h light/dark cycle. Animal were administered intravenous (i.v.) injections of 5-FU (25 mg/kg) 5 times every 3 days starting on day 9 of the experiment. The rats were divided into preventive, recovery, and throughout groups and co-treated with melatonin (8 mg/kg, i.p.) once daily (at 7.00 pm) for 21 days prior to, after, and throughout 5-FU treatment, respectively. Spatial memory was assessed using a novel object location (NOL) test. Hippocampal neurogenesis was then examined using Ki67, bromodeoxyuridine (BrdU), and doublecortin (DCX) immunohistochemistry staining. KEY FINDINGS: Melatonin administration was able to both protect the subjects from and reverse spatial memory deficits. 5-FU was also found to reduce the generation of hippocampal newborn neurons. However, co-treatment with melatonin ameliorated the reductions in neurogenesis caused by 5-FU. SIGNIFICANCE: These findings suggest that melatonin administration was able to ameliorate the 5-FU-induced spatial memory deficits associated with neurogenesis. The present work will be valuable for patients who suffer memory deficits from 5-FU chemotherapy.
AIMS: Treatment with 5-fluorouracil (5-FU) can cause impairment to adult hippocampal neurogenesis, resulting in cognitive deficits. As melatonin has been shown to enhance memory and hippocampal neurogenesis in animal models, this research investigated the neuroprotective effects of melatonin against spatial memory and hippocampal neurogenesis impairment in 5-fluorouracil (5-FU)-treated rats. MATERIALS AND METHODS: Four-Five weeks old male Spraque-Dawley rats weighing between 180 and 200 g were used. Animals were maintained under standard laboratory conditions with 25 °C and 12 h light/dark cycle. Animal were administered intravenous (i.v.) injections of 5-FU (25 mg/kg) 5 times every 3 days starting on day 9 of the experiment. The rats were divided into preventive, recovery, and throughout groups and co-treated with melatonin (8 mg/kg, i.p.) once daily (at 7.00 pm) for 21 days prior to, after, and throughout 5-FU treatment, respectively. Spatial memory was assessed using a novel object location (NOL) test. Hippocampal neurogenesis was then examined using Ki67, bromodeoxyuridine (BrdU), and doublecortin (DCX) immunohistochemistry staining. KEY FINDINGS:Melatonin administration was able to both protect the subjects from and reverse spatial memory deficits. 5-FU was also found to reduce the generation of hippocampal newborn neurons. However, co-treatment with melatonin ameliorated the reductions in neurogenesis caused by 5-FU. SIGNIFICANCE: These findings suggest that melatonin administration was able to ameliorate the 5-FU-induced spatial memory deficits associated with neurogenesis. The present work will be valuable for patients who suffer memory deficits from 5-FU chemotherapy.
Authors: Anna Kurowska; Iwona Bodys-Cupak; Magdalena Staszkiewicz; Joanna Szklarczyk; Joanna Zalewska-Puchała; Anna Kliś-Kalinowska; Marta Makara-Studzińska; Anna Majda Journal: Int J Environ Res Public Health Date: 2020-05-21 Impact factor: 3.390