Melatonin attenuates the high-fat diet and streptozotocin-induced reduction in rat hippocampal neurogenesis.
A deviant level of melatonin in blood circulation has been associated with the development of diabetes and with learning and memory deficiencies. Melatonin might have an important function in diabetes control; however, the mechanism of melatonin in diabetes remains unknown. The present study aimed to investigate the hyperglycemic condition induced by high-fat diet (HFD) feeding and streptozotocin (STZ) injection and to examine the effect of melatonin on adult hippocampal functions. HFD-fed and STZ-treated rats significantly increased blood glucose level. The present study showed that HFD-fed and STZ-treated rats significantly impaired memory in the Morris Water Maze task, reduced neurogenesis in the hippocampus shown by a reduction in nestin, doublecortin (DCX) and β-III tubulin immunoreactivities, reduced axon terminal markers, synaptophysin, reduced dendritic marker including postsynaptic density 95 (PSD-95) and the glutamate receptor subunit NR2A. Moreover, a significant downregulation of melatonin receptor, insulin receptor-β (IR-β) and both p-IR-β and phosphorylated extracellular signal-regulated kinase (p-ERK) occurred in HFD-fed and STZ-treated rats, while the level of glial fibrillary acidic protein (GFAP) increased. Treatment of melatonin, rats had shorter escape latencies and remained in the target quadrant longer compared to the HFD-fed and STZ-treated rats. Melatonin attenuated the reduction of neurogenesis, synaptogenesis and the induction of astrogliosis. Moreover, melatonin countered the reduction of melatonin receptor, insulin receptor and downstream signaling pathway for insulin. Our data suggested that the dysfunction of insulin signaling pathway occurred in the diabetes may provide a convergent mechanism of hippocampal impaired neurogenesis and synaptogenesis lead to impair memory while melatonin reverses these effects, suggesting that melatonin may reduce the pathogenesis of diabetes.
Center for Research and Innovation, Faculty of Medical Technology, Mahidol University, Salaya, Nakon Pathom, 73170, Thailand.
Prapimpun
P
Wongchitrat
Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Salaya, Nakon Pathom, 73170, Thailand; Department of Anatomy, Faculty of Veterinary Medicine, Kasetsart University, Bangkok, 10900, Thailand.
Niyada
N
Lansubsakul
Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Salaya, Nakon Pathom, 73170, Thailand.
Utcharaporn
U
Kamsrijai
Innovative Learning Center, Srinakharinwirot University, Bangkok, 10110, Thailand.
Kwankanit
K
Sae-Ung
Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Salaya, Nakon Pathom, 73170, Thailand.
Sujira
S
Mukda
Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Salaya, Nakon Pathom, 73170, Thailand; Center for Neuroscience and Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand. Electronic address: piyarat.gov@mahidol.ac.th.
Piyarat
P
Govitrapong
D000818:Animals; D059305:Diet, High-Fat; D000089662:Doublecortin Protein; D006624:Hippocampus / Q000378:metabolism*; D006943:Hyperglycemia / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects*; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000378:metabolism; D013311:Streptozocin / Q000494:pharmacology*; D016708:Synaptophysin / Q000378:metabolism
C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D017470:Receptors, Glutamate; D016708:Synaptophysin; D013311:Streptozocin; D008550:Melatonin
Diabetes; Hippocampus; Insulin receptors; Melatonin receptors; Neurogenesis; Synaptogenesis