Abstract
Type 2 diabetes mellitus (T2DM) is known to be associated with an increased risk of dementia, specifically Alzheimer’s disease and vascular dementia. Intermittent fasting (IF) has been proposed to produce neuroprotective effects through the activation of several signaling pathways. In this study, we investigated the effect of IF on rat behavior in type 2 diabetic rats. Forty male Wistar Kyoto rats were divided into four groups (n = 10 for each): the ad libitum (Ad) group, the intermittent fasting group (IF), the streptozotocin-induced diabetic 2 group (T2DM) fed a high-fat diet for 4 weeks followed by a single intraperitoneal (i.p.) injection of streptozotocin (STZ) 25 mg kg−1, and the diabetic group with intermittent fasting (T2DM+IF). We evaluated the impact of 3 months of IF (16 h of food deprivation daily) on the levels of brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), serotonin, dopamine, and glutamate in the hippocampus, and rat behavior was assessed by the forced swim test and elevated plus maze. IF for 12 weeks significantly increased (p < 0.05) the levels of NT3 and BDNF in both control and T2DM rats. Additionally, it increased serotonin, dopamine, and glutamic acid in diabetic rats. Moreover, IF modulated glucose homeostasis parameters, with a significant decrease (p < 0.05) in insulin resistance and downregulation of serum corticosterone level. Interestingly, T2DM rats showed a significant increase in anxiety and depression behaviors, which were ameliorated by IF. These findings suggest that IF could produce a potentially protective effect by increasing the levels of BDNF and NT3 in both control and T2DM rats. IF could be considered as an additional therapy for depression, anxiety, and neurodegenerative diseases.
Highlights
Recent evidence suggests that metabolic syndrome and type 2 diabetes mellitus (T2DM) are associated with changes in cognitive function, as well as memory [1,2]
T2DM is comorbid with depression, and it has been reported that depressive states are twice as common in diabetic patients than in the general population
All rats were provided from the animal house in Sultan Qaboos University (SQU) where they were kept under controlled conditions (23 ± 1 ◦ C, 12 h light:12 h dark cycle)
Summary
Recent evidence suggests that metabolic syndrome and type 2 diabetes mellitus (T2DM) are associated with changes in cognitive function, as well as memory [1,2]. Impaired insulin signaling is considered the main etiology in the pathogenesis of diabetic cognitive impairment, [7] as well as increased inflammatory and oxidative stress pathways [8]. It has been stated that insulin receptor functioning is reduced in AD patients. Reduced insulin receptors expression, as well as desensitization or alterations to their intracellular signaling pathways, have been reported. T2DM is comorbid with depression, and it has been reported that depressive states are twice as common in diabetic patients than in the general population. It has been suggested that depression and T2DM share biological origins, such as an abnormal cytokine-mediated inflammatory response, with hyper activation of innate immunity and over stimulationof the hypothalamo-pituitary adrenal (HPA) axis [9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
