Resveratrol prevents cognitive deficits by attenuating oxidative damage and inflammation in rat model of streptozotocin diabetes induced vascular dementia

Göçmez, S.S.; Şahin, Tuğçe Demirtaş; Yazır, Yusufhan; Duruksu, Gökhan; Eraldemir, Fatma Ceyla; Polat, Selen; Utkan, Tijen

doi:10.1016/j.physbeh.2018.12.012

Cited by 62 publications

(43 citation statements)

References 47 publications

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“…38,39 Some studies have used RSV to reverse the cognitive deficits caused by diabetes in rats. 40,41 Consistent with these findings, our study showed that 4 months of RSV treatment significantly reduced the escape latency of T2DM mice and increased the number of crossings and time spent in the target quadrant (Figure 2A-C). In addition, RSV significantly improved T2DM-induced hippocampal neuronal cell damage and synaptic ultrastructure damage ( Figure 3A and B).…”

Section: Dovepresssupporting

confidence: 85%

<p>Resveratrol Prevents Cognitive Impairment in Type 2 Diabetic Mice by Upregulating Nrf2 Expression and Transcriptional Level</p>

Wang

Fang

et al. 2020

DMSO

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Purpose: This study aimed to determine whether the natural antioxidant resveratrol (RSV) prevents type 2 diabetes mellitus (T2DM)-induced cognitive impairment and to explore whether redox-associated factor nuclear factor erythroid 2-related factor 2 (Nrf2) plays a critical role in the neuroprotective effect of RSV. Materials and Methods: We established a T2DM model with 8-week-old male ICR mice by administration of a high-fat diet for 2 months and low-dose streptozotocin for 3 days. Then, diabetic and age-matched control mice were treated with or without RSV for 4 months every other day and subjected to the Morris water maze test. After the mice were euthanized, whole brains were sectioned for Nissl staining and immunofluorescence labeling. Hippocampal sections were observed by transmission electron microscopy to evaluate the ultrastructure of synapses. Inflammatory factors, oxidative stress-related indexes, and Nrf2 and downstream target gene expression were analyzed in hippocampal tissues by quantitative real-time PCR, Western blotting, and associated quantitative kits. Results: In the Morris water maze test, compared to control mice, T2DM mice showed learning and memory impairments, but RSV treatment prevented the learning and memory decline in T2DM mice. Similarly, RSV prevented T2DM-induced hippocampal neuron destruction and synaptic ultrastructural damage. The expression levels of inflammatory factors and oxidative stress-related indicators were increased in the T2DM group compared with the control group but were decreased significantly by RSV treatment in the T2DM group. Additionally, the expression of Nrf2 and its downstream target genes was decreased in the T2DM group compared with the control group and was significantly increased by RSV treatment in the T2DM group. Conclusion: RSV prevented T2DM-induced cognitive impairment through anti-inflammatory and antioxidant activities. This effect was accompanied by the upregulation of Nrf2 transcriptional activity and the increased expression of downstream antioxidant genes.

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Section: Dovepresssupporting

confidence: 85%

<p>Resveratrol Prevents Cognitive Impairment in Type 2 Diabetic Mice by Upregulating Nrf2 Expression and Transcriptional Level</p>

Wang

Fang

et al. 2020

DMSO

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“…Consistent with these clinical studies, our results proved that repeated administration of METH caused significant memory deficits after 7 days and 22 days post‐injection, indicating a long‐lasting memory impairment behavior. Resveratrol is an effective natural product that could inhibit the generation of free radicals, reduce oxidative stress‐induced neuronal damage, and ameliorate cognitive impairment (Gocmez et al., 2019; Wang et al., 2019; Zhang et al., 2019). Resveratrol has been reported to be protective against METH damage in cultured cells in vitro, however, its effect on METH damage in vivo is also worth further study.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol attenuates methamphetamine‐induced memory impairment via inhibition of oxidative stress and apoptosis in mice

et al. 2021

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Methamphetamine (METH) abuse produces serious neurotoxicity to the central nervous system along with long-term cognitive dysfunction. Resveratrol, a natural polyphenol, has broad application prospects in the treatment of neurodegenerative diseases. Therefore, this study was conducted to investigate whether resveratrol might alleviate METH-induced memory deficits in vivo. We found that multiple exposures to METH significantly impaired cognitive functions and caused long-lasting memory deficits (p < .05). Pretreatment of resveratrol (10 or 100 mg/kg) remarkably attenuated METH-induced memory impairment in mice (p < .05). Bioinformatics analysis results showed that resveratrol might alleviate memory deficits by inhibiting METH-induced oxidative damage and apoptosis. Molecular docking showed that resveratrol had hydrogen bonding interactions with Kelch-like ECH associated protein 1 (Keap1), a repressor protein of the classic antioxidant Keap1-Nrf2 pathway. Further results validated oxidative stress parameters, apoptosis, and expression of Keap1 were significantly increased, while the translocation and activation of nuclear factor erythroid 2-related factor 2 (Nrf2) into the nucleus and expression of its downstream proteins were greatly decreased in the hippocampus after METH exposure (p < .05). These changes caused by METH could be prevented by resveratrol (p < .05). Therefore, these findings suggested that the prevention of resveratrol on memory dysfunction induced by METH was possibly related to the activation of the Keap1-Nrf2 pathway and reduction of apoptosis. Supplementation of resveratrol could be a potential treatment for preventing the neurotoxicity of METH in the future. Practical applications As one of the worst commonly abused psychostimulants, methamphetamine (METH) addiction produces serious complications including cognitive impairment and memory deficits. Resveratrol is a natural polyphenol that has important nutritional supplements and protective effects in the treatment of many neurodegenerative diseases.

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“…ASK1 is a crucial facilitator and therapeutic target for preventing brain injury associated with obesity (Toyama et al, 2015). Excessive oxidative stress in the hippocampus has been reported as a critical contributing factor for diabetes-induced cognitive dysfunction (Davari et al, 2013;Adedara et al, 2019;Gocmez et al, 2019). However, it is unknown whether ASK1-JNK1/2 signaling is involved in diabetes-triggered hippocampal neuronal apoptosis, and its mutual regulatory relationship with ER stress during DICD is also not well understood.…”

Section: Introductionmentioning

confidence: 99%

The Reciprocal Causation of the ASK1-JNK1/2 Pathway and Endoplasmic Reticulum Stress in Diabetes-Induced Cognitive Decline

Yuan

et al. 2020

Front. Cell Dev. Biol.

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Diabetes significantly induces cognitive dysfunction. Neuronal apoptosis is the main cause of diabetes-induced cognitive decline (DICD). Apoptosis signal-regulating kinase 1 (ASK1) and endoplasmic reticulum (ER) stress are remarkably activated by diabetes. The role and relationship of ASK1-JNK1/2 signaling and ER stress in DICD have not yet been elucidated. In this study, we used db/db mice as the DICD animal model and confirmed that db/db mice displayed cognitive decline with inferior learning and memory function. Diabetes significantly induced morphological and structural changes, excessive neuronal apoptosis, Aβ 1−42 large deposition, and synaptic dysfunction in the hippocampus. Mechanistic studies found that diabetes significantly triggered ASK1-JNK1/2 signaling activation and increased ER stress in the hippocampus. Moreover, diabetes enhanced the formation of the IRE1α-TRAF2-ASK1 complex, which promotes the crosstalk of ER stress and the ASK1-JNK1/2 pathway during DICD. Furthermore, 4-PBA treatment blocked high glucose (HG)-induced ASK1-JNK1/2 signaling activation, and excessive apoptosis in vitro. Inhibiting ASK1 via siRNA remarkably ameliorated the HG-induced increase in p-IRE1α and associated apoptosis in SH-SY5Y cells, suggesting that ASK1 is essential for the assembly and function of the proapoptotic kinase activity of the IRE1α signalosome. In summary, ER stress and ASK1-JNK1/2 signaling play causal roles in DICD development, which has crosstalk through the formation of the IRE1α-TRAF2-ASK1 complex.

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Resveratrol prevents cognitive deficits by attenuating oxidative damage and inflammation in rat model of streptozotocin diabetes induced vascular dementia

Cited by 62 publications

References 47 publications

<p>Resveratrol Prevents Cognitive Impairment in Type 2 Diabetic Mice by Upregulating Nrf2 Expression and Transcriptional Level</p>

<p>Resveratrol Prevents Cognitive Impairment in Type 2 Diabetic Mice by Upregulating Nrf2 Expression and Transcriptional Level</p>

Resveratrol attenuates methamphetamine‐induced memory impairment via inhibition of oxidative stress and apoptosis in mice

The Reciprocal Causation of the ASK1-JNK1/2 Pathway and Endoplasmic Reticulum Stress in Diabetes-Induced Cognitive Decline

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