Background/Aims: To explore the effects of sulforaphane (SFN) on neuronal apoptosis in hippocampus and memory impairment in diabetic rats. Methods: Thirty male rats were randomly divided into normal control, diabetic model and SFN treatment groups (N = 10 in each group). Streptozotocin (STZ) was applied to establish diabetic model. Water Morris maze task was applied to test learning and memory. Tunel assaying was used to detect apoptosis in hippocampus. The expressions of Caspase-3 and myeloid cell leukemia 1(MCL-1) were detected by western blotting. Neurotrophic factor levels and AKT/GSK3β pathway were also detected. Results: Compared with normal control, learning and memory were apparently impaired, with up-regulation of Caspase-3 and down-regulation of MCL-1 in diabetic rats. Apoptotic neurons were also found in CA1 region after diabetic modeling. By contrast, SFN treatment prevented the memory impairment, decreased the apoptosis of hippocampal neurons. SFN also attenuated the abnormal expression of Caspase-3 and MCL-1 in diabetic model. Mechanically, SFN treatment reversed diabetic modeling-induced decrease of p-Akt, p-GSK3β, NGF and BDNF expressions. Conclusion: SFN could prevent the memory impairment and apoptosis of hippocampal neurons in diabetic rat. The possible mechanism was related to the regulation of neurotropic factors and Akt/GSK3β pathway.
The purpose of the present study was to study the effects of resveratrol on cognitive function in rats with vascular dementia and to investigate the molecular mechanisms of its neuroprotective effects. Forty-five SD rats were randomly divided into 3 groups: The control group (Con group, n=15), the model group (VD group, n=15) and the resveratrol-treated VD group (Res group, n=15). The VD rats (the VD group and the Res group) were generated by bilateral common carotid artery occlusion. The rats in the Res group received daily resveratrol treatment intraperitoneally for 4 weeks. Cognitive function was tested using the Morris water maze test. The levels of SOD and MDA (oxidative stress indicators) were detected by ELISA kits. The protein expression of Bax, Bcl-2 and caspase-3 was detected by western blotting. Compared with the rats in the Con group, the rats in the VD group exhibited decreased cognitive function, significantly increased hippocampal content of MDA, Bax and caspase-3 (P<0.05), and significantly reduced hippocampal expression of SOD and Bcl-2 (P<0.05). Compared with the rats in the VD group, the rats in the Res group exhibited increased cognitive ability, reduced hippocampal content of MDA, Bax and caspase-3 (P<0.05), and increased hippocampal expression of SOD and Bcl-2 (P<0.05). Resveratrol treatment significantly improved the spatial learning and memory of the VD rats. The mechanism associated with the neuroprotective effects of resveratrol may be closely related to the inhibition of the apoptosis pathway and oxidative stress injury.
BackgroundHuman umbilical cord blood derived-mesenchymal stem cells (hUCMSCs) offer an attractive alternative to bone marrow-derived MSCs (BMMSCs) for cell-based therapy as it is a less invasive source of biological material. However, limited studies have been conducted with hUCMSCs as compared to BMMSCs. The present study was conducted to evaluate the effects of hUCMSCs in esophageal carcinoma (EC).MethodshUCMSCs together with EC cells were transplanted subcutaneously into BALB/c nude mice to observe the effects of hUCMSCs on tumor establishment. hUCMSCs injected through the caudal vein to the mice with pre-established EC to observe the effects of hUCMSCs on tumor outgrowth. In order to elucidate the underlying mechanisms, we also performed in vitro experiments including directly co-culture, transwell assay, proliferation assay and western blotting analysis.ResultshUCMSCs promoted EC formation in nude mice. In the in vivo model of pre-established EC, intravenously injected hUCMSCs potently promoted tumor growth. When in vitro co-cultured with hUCMSCs, EC cells proliferation increased. After co-cultured with hUCMSCs through transwell system, EC cells showed increased proliferation. Through transwell assay, we also observed that EC cells recruited MSCs, and MSCs promoted EC cells migration and invasion. Western blotting data showed that the expressions of proliferation related proteins Bcl-2, survivin and metastasis related proteins MMP-2 and MMP-9 were up-regulated in the EC cells transwell co-cultured with hUCMSCs.ConclusionsOur results indicated that hUCMSCs could favor tumor growth in vivo and in vitro. Thus, the exploitation of hUCMSCs in new therapeutic strategies should be cautious under the malignant conditions.
Type 2 diabetes mellitus (T2DM) markedly impairs human health. During T2DM development, some patients experience cognitive dysfunction and behavioral deficits, which are characterized by neuronal injury and memory loss. It has been reported that the incidence of dementia in middle-aged and elderly patients with diabetes is significantly higher than that in normal elderly patients. Currently, the pathogenesis of cognitive dysfunction in diabetes remains unknown, and there is no standard or specific method to diagnose the disease in clinical practice. Evidence has shown that fish oil (FO) can alleviate depressive-like behaviors by attenuating neuroinflammation in a rat model, and improve cognitive dysfunction by inhibiting apoptosis. Therefore, it is reasonable to speculate that FO may reduce cognitive impairment by attenuating neuroinflammation in diabetic rats. In the present study, we investigated the effects of FO supplementation on cognitive dysfunction in a streptozotocin-induced diabetic rat model. FO administration for 10 weeks improved spatial learning and memory as evaluated by performance in the Morris water maze (MWM). Besides, FO significantly improved the morphology of neurons in the hippocampus and cortex of diabetic rats and reduced the neuronal nuclear condensation. Moreover, FO decreased the mRNA expression of IL-1β, IL -6, and TNF-α and increased the mRNA expression of IL-4 and IL-10 in the cortex and hippocampus. FO also attenuated the brain inflammatory cascade and simultaneously reduced diabetes-induced oxidative stress. In addition, FO increased the protein expression of Nrf2 and HO-1 in cortex and hippocampus of diabetic rats. These results provide a novel horizon for the study of neuroprotective effect of FO and further clarify the connections among inflammation, oxidative stress and diabetes-induced cognitive impairment.
exenatide could reduce blood glucose and alleviate cognitive dysfunction induced by diabetes mellitus (dM). in the present study, a diabetic model was established in Sprague-dawley rats to further explore the mechanism of exenatide on diabetes-induced cognitive impairment. notably, the model rats performed poorly in the Morris water maze test and had more apoptotic neurons compared with the control rats. By contrast, exenatide attenuated cognitive impairment and inhibited neuronal apoptosis in the dM rat model. To explore the neuroprotective mechanisms of exenatide, western blotting was performed to detect the expression levels of markers of endoplasmic reticulum stress, including cytochrome c (cyt-c), caspase-3, JnK and c-Jun, in hippocampal tissue. reverse transcription-quantitative Pcr was also performed to measure the mrna expression levels of cyt-c and caspase-3. after 16 weeks of treatment, exenatide treatment downregulated cyt-c, caspase-3, phosphorylated (p)-JnK and p-c-Jun expression in the hippocampal tissue of diabetic rats. Moreover, cyt-c, caspase-3, JnK and Jun expression levels were detected following treatment with a specific inhibitor of JNK (SP600125). The results revealed that SP600125 had similar inhibitory effects on the JnK pathway and erS-related protein expression (cyt-t, caspase-3, p-JnK and p-c-Jun). These results suggested that exenatide improved cognitive dysfunction in dM rats and that the underlying mechanism may be associated with inhibiting apoptosis by suppressing the activation of JnK/c-Jun.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.