Evaluation of the Role of Melatonin in Dietary Restriction Effects on Spatial Memory Impairment Induced by Streptozotocin (STZ) in Male Rats

Document Type : Original Articles


1 Department of Physiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran

2 Department of Physiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran

3 Histomorphometry and Stereology research center, Shiraz University of Medical Sciences, Shiraz, Iran; Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran


Background: It has been shown that dietary restriction in the form of every other day fasting (EODF) has neuroprotective effects. The mechanisms of these effects are unknown yet. Recently, it has claimed that dietary restriction can reset circadian and regulate irregular rhythms. Previous studies have demonstrated that dietary restriction can change melatonin production and secretion. Since melatonin has important role in circadian rhythms and its neuroprotective effect has been proved, it is reasonable that at least some dietary restriction effects may be due to the melatonin level changes. To investigate this hypothesis, melatonin receptors antagonist (Luzindole) was used in the rat model of Alzheimer’s disease. Material and Methods: Sixty four male rats were assigned into 8 groups which 4 groups had Ad libitum and 4 groups had every other day fasting (EODF) diet. Each group category comprised: 1-control group receiving only solvent of drugs, 2-group which received streptozotocin (STZ) at 3 mg/kg/icv,  3-group which received STZ at 3 mg/kg/icv and luzindole 50 µgr/kg/icv and 4-group which received STZ 3 mg/kg/icv and melatonin 10 mg/kg/ip. Dietary regimen continued for 10 days from the day cannulation was done in lateral ventricles. Spatial memory was evaluated by Morris water maze test. To evaluate the histological changes in the brain tissue, hematoxylin and eosin staining was used. Results: Based on Morris water maze test results, STZ could impair spatial memory in rats while dietary restriction did not improve memory impairment significantly. Likewise, melatonin and luzindole could not restore memory impairment. Histological study indicated that STZ destroyed the brain tissue in different parts including paraventricular zone, fornix, cortex and hippocampus which could be attributed to memory impairment. Counting dead neurons in CA1 part of the hippocampus showed that dietary restriction accompanied by exogenous melatonin with supra physiological dose, could partially improve STZ-induced impact in brain tissue. Conclusion: Melatonin appears not to retain an important role in the effects of dietary restriction on spatial memory impairment. Meanwhile, dietary restriction associated with exogenous melatonin seem to exert neuroprotective effects.


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