Insulin resistance-induced hyperglycemia decreased the activation of Akt/CREB in hippocampus neurons: Molecular evidence for mechanism of diabetes-induced cognitive dysfunction

Xiang, Qian; Zhang, Jie; Li, Chunyan; Wu, Yan; Zeng, Mao-Jun; Cai, Z. Y.; Tian, Rong-Bo; Jia, Weiping; Li, Xianhui

doi:10.1016/j.npep.2015.08.009

Cited by 62 publications

(38 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…On the one hand, neurotrophic factors were decreased after STZ injection. The decrease of neurotrophic factors have been confirmed to regulate the neuronal survival and might partially explain the pyramid neuronal loss [22].…”

Section: Discussionmentioning

confidence: 98%

Sulforaphane Prevents Neuronal Apoptosis and Memory Impairment in Diabetic Rats

Wang

Fang

Zhen

et al. 2016

Cell Physiol Biochem

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 98%

Sulforaphane Prevents Neuronal Apoptosis and Memory Impairment in Diabetic Rats

Wang

Fang

Zhen

et al. 2016

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…In the diabetic rats in the present study, STZ-induced persistent hyperglycemia is associated with cognitive dysfunction. The positive correlation between persistent hyperglycemia and cognitive dysfunction was also found in STZ-induced diabetic mice and spontaneously diabetic Goto-Kakizaki (GK) rats [31, 48]. Several DM hyperglycemia ameliorating drugs such as the peroxisome proliferator-activated receptor gamma (PPARγ) agonist, glucagon-like peptide-1 (GLP-1) and dipeptidylpeptidase-4 inhibitor were reported to improve the cognitive deficits in DM patients [49–51].…”

Section: Discussionmentioning

confidence: 99%

High glucose induces formation of tau hyperphosphorylation via Cav-1-mTOR pathway: A potential molecular mechanism for diabetes-induced cognitive dysfunction

Zhou

et al. 2017

Oncotarget

View full text Add to dashboard Cite

The abnormally hyperphosphorylated tau is thought to be implicated in diabetes-associated cognitive deficits. The role of mammalian target of rapamycin (mTOR) / S6 kinase (S6K) signalling in the formation of tau hyperphosphorylation has been previously studied. Caveolin-1 (Cav-1), the essential structure protein of caveolae, promotes neuronal survival and growth, and inhibits glucose metabolism. In this study, we aimed to investigate the role of Cav-1 in the formation of tau hyperphosphorylation under chronic hyperglycemic condition (HGC). Diabetic rats were induced by streptozotocin (STZ). Primary hippocampal neurons with or without molecular intervention such as the transient over-expression or knock-down were subjected to HGC. The obtained experimental samples were analyzed by real time quantitative RT-PCR, Western blot, immunofluorescence or immunohistochemisty. We found: 1) that a chronic HGC directly decreases Cav-1 expression, increases tau phosphorylation and activates mTOR/S6K signalling in the brain neurons of diabetic rats, 2) that overexpression of Cav-1 attenuates tau hyperphosphorylation induced by chronic HGC in primary hippocampal neurons, whereas down-regulation of Cav-1 using Cav-1 siRNA dramatically worsens tau hyperphosphorylation via mTOR/S6K signalling pathway, and 3) that the down-regulation of Cav-1 induced by HGC is independent of mTOR signalling. Our results suggest that tau hyperphosphorylation and the sustained over-activated mTOR signalling under hyperglycemia may be due to the suppression of Cav-1. Therefore, Cav-1 is a potential therapeutic target for diabetes-induced cognitive dysfunction.

show abstract

“…Moreover, recent reports in animal models with DM‐induced by streptozotocin have shown that continuous hyperglycemia leads to damage at the neuronal level (Georgy, et al, ; Lazcano et al, ; Martinez‐Tellez et al, ; Sanchez‐Vega et al, ; Shingo et al, ). High levels of glycemia may produce dendritic atrophy with a reduced number of dendritic spines at the level of pyramidal neurons of the PFC and the hippocampus in the rats (Brocca et al, ; Joghataie et al, ; Lazcano et al, ; Martinez‐Tellez et al, ; Shingo et al, ; Xiang et al, ) and mice (Beauquis et al, ; Malone et al, ; Sanchez‐Vega et al, ; Taylor et al, ) (see Table ). In addition, db/db mice, an animal model of diabetes mellitus type 2, also showed a reduced number of dendritic spines in the pyramidal neurons of the PFC and CA1 of the hippocampus and the granule cells of the dentate gyrus (DG) of the hippocampus (Chen et al, ; Stranahan et al, ; Wang et al, ) (see Table ).…”

Section: Neural Transmission In Animal Model Of Dmmentioning

confidence: 99%

“…Furthermore, at the level of the brain, other disorders such as cerebrovascular stroke, autonomic neuropathies, cognitive deficits, and depression present together with DM further complications (for review see Hamed, ). As mentioned before, several reports from our group and other groups have demonstrated that high levels of glycemia and/or blood artery pressure may produce dendritic atrophy of the pyramidal neurons of the PFC and the hippocampus (Chen et al, ; Lazcano et al, ; Malone et al, ; Martinez‐Tellez et al, ; Sanchez et al, ; Sanchez‐Vega et al, ; Solis‐Gaspar et al, ; Shingo et al, ; Taylor et al, ; Xiang et al, ; Vega et al, ). However, how high glucose levels are able to damage the dendritic tree and reduce spinogenesis in limbic regions such as the PFC and the hippocampus at this moment is not clear.…”

Section: Relevance Of Neuronal Morphology In Diabetesmentioning

confidence: 99%

Consequences of diabetes mellitus on neuronal connectivity in limbic regions

Flores-Gómez

Gómez-Villalobos

Flores

2018

Synapse

View full text Add to dashboard Cite

Diabetes mellitus (DM) is characterized by high levels of blood glucose. In recent years, its prevalence has increased, which was 422 million in the world in 2014. In elderly patients, DM is associated with deficits in memory and learning processes. The cognitive deficits lead to dementia. With the development of animal models in DM, it has been possible to better understand quantitative morphological changes in numerous neuronal structures belonging to the limbic system, such as the prefrontal cortex (PFC), the hippocampus and basolateral amygdala (BLA). These structures are in close relationship with processes of memory and learning. Several reports have demonstrated that chronic hyperglycemia reduces spinogenesis and dendritic arborization in the aforementioned regions along with a decline in memory and learning processes, especially in streptozotocin (STZ)‐induced diabetic rats. In the present review, we discuss animal models, the effects of chronic hyperglycemia on dendritic morphology of limbic regions and memory and learning processes, the effect on neural transmission in these regions, the pathologic mechanisms involved, and the relevance of dendritic morphology in diabetes. All of this information can help us to have a better understanding of dementia in diabetes mellitus and propose strategies for its prevention and treatment.

show abstract

Insulin resistance-induced hyperglycemia decreased the activation of Akt/CREB in hippocampus neurons: Molecular evidence for mechanism of diabetes-induced cognitive dysfunction

Cited by 62 publications

References 27 publications

Sulforaphane Prevents Neuronal Apoptosis and Memory Impairment in Diabetic Rats

Sulforaphane Prevents Neuronal Apoptosis and Memory Impairment in Diabetic Rats

High glucose induces formation of tau hyperphosphorylation via Cav-1-mTOR pathway: A potential molecular mechanism for diabetes-induced cognitive dysfunction

Consequences of diabetes mellitus on neuronal connectivity in limbic regions

Contact Info

Product

Resources

About