Blood glucose regulation mechanism in depressive disorder animal model during hyperglycemic states

Lim, Seungyup; Park, Soo-Hyun; Sharma, Naveen; Kim, Sung‐Su; Lee, Jae Ryeong; Jung, Jun‐Sub; Suh, Hwal

doi:10.1016/j.brainresbull.2016.03.014

Cited by 12 publications

(14 citation statements)

References 29 publications

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“…Besides, similar CUMS-induced depressive co-morbid glucose intolerant phenotypes were also observed in some other studies and could be reversed by rosiglitazone, umbelliferone and curcumin [ 51 – 53 ]. In contrast, another recent work reported down-regulated blood glucose in depression mouse model [ 54 ]. Indeed, during the preclinical period of T2D, hyperinsulinemia and β-cell hyperplasia were often developed to compensate for insulin resistance [ 55 ].…”

Section: Discussionmentioning

confidence: 93%

Antidiabetic drug glyburide modulates depressive-like behavior comorbid with insulin resistance

Wei

Gong

et al. 2017

J Neuroinflammation

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BackgroundAbundant reports indicated that depression was often comorbid with type 2 diabetes and even metabolic syndrome. Considering they might share common biological origins, it was tentatively attributed to the chronic cytokine-mediated inflammatory response which was induced by dysregulation of HPA axis and overactivation of innate immunity. However, the exact mechanisms remain obscure. Herein, we mainly focused on the function of the NLRP3 inflammasome to investigate this issue.MethodsMale C57BL/6 mice were subjected to 12 weeks of chronic unpredictable mild stress (CUMS), some of which were injected with glyburide or fluoxetine. After CUMS procedure, behavioral and metabolic tests were carried out. In order to evaluate the systemic inflammation associated with inflammasome activation, IL-1β and inflammasome components in hippocampi and pancreases, as well as corticosterone and IL-1β in serum were detected separately. Moreover, immunostaining was performed to assess morphologic characteristics of pancreases.ResultsIn the present study, we found that 12 weeks’ chronic stress resulted in depressive-like behavior comorbid with insulin resistance. Furthermore, antidiabetic drug glyburide, an inhibitor of the NLRP3 inflammasome, was discovered to be effective in preventing the experimental comorbidity. In brief, it improved behavioral performance, ameliorated insulin intolerance as well as insulin signaling in the hippocampus possibly through inhibiting NLRP3 inflammasome activation by suppressing the expression of TXNIP.ConclusionsAll these evidence supported our hypothesis that chronic stress led to comorbidity of depressive-like behavior and insulin resistance via long-term mild inflammation. More importantly, based on the beneficial effects of blocking the activation of the NLRP3 inflammasome, we provided a potential therapeutic target for clinical comorbidity and a new strategy for management of both diabetes and depression.

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Section: Discussionmentioning

confidence: 93%

Antidiabetic drug glyburide modulates depressive-like behavior comorbid with insulin resistance

Wei

Gong

et al. 2017

J Neuroinflammation

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“…Oga +/− mice exhibit antidepressant-like behaviors. A deficit in glucose metabolism leads to an increased risk for neuropsychiatric diseases, such as depression and anxiety, and patients with depressive disorders exhibit reduced glucose metabolic activity in the mPFC [20][21][22][23] . In addition, elevated blood glucose levels induced by a high-fat diet have been shown to modulate depression and anxiolytic-like behaviors 36 .…”

Section: Resultsmentioning

confidence: 99%

“…Glucose is a major energy source in the brain 20 and, notably, impaired glucose metabolism is strongly associated with major depressive disorders [20][21][22] . For example, in patients with depressive disorder who showed metabolic abnormalities in the prefrontal cortex region, the administration of antidepressant drugs restored the glucose metabolism 23 .…”

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confidence: 99%

Elevated O-GlcNAcylation induces an antidepressant-like phenotype and decreased inhibitory transmission in medial prefrontal cortex

Cho

Hwang

Rahman

et al. 2020

Sci Rep

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Depression is a devastating mental disorder affected by multiple factors that can have genetic, environmental, or metabolic causes. Although previous studies have reported an association of dysregulated glucose metabolism with depression, its underlying mechanism remains elusive at the molecular level. A small percentage of glucose is converted into uridine diphosphate-Nacetylglucosamine (UDP-GlcNAc) via the hexosamine biosynthetic pathway, which serves as an immediate donor for protein O-GlcNAc modification. O-GlcNAcylation is a particularly common posttranslational modification (PTM) in the brain, and the functional significance of O-GlcNAcylation in neurodegenerative diseases has been extensively reported. However, whether the degree of O-GlcNAc modification is associated with depressive disorder has not been examined. In this study, we show that increased o-GlcnAcylation levels reduce inhibitory synaptic transmission in the medial prefrontal cortex (mPFC), and that Oga +/− mice with chronically elevated o-GlcnAcylation levels exhibit an antidepressant-like phenotype. Moreover, we found that virus-mediated expression of OGA in the mPFC restored both antidepressant-like behavior and inhibitory synaptic transmission. Therefore, our results suggest that O-GlcNAc modification in the mPFC plays a significant role in regulating antidepressant-like behavior, highlighting that the modulation of O-GlcNAcylation levels in the brain may serve as a novel therapeutic candidate for antidepressants. Depressive disorder is a devastating mental disorder characterized by symptoms such as loss of interest, low mood, fatigue, and diminished cognitive functions 1-3. A deficit in monoamine metabolism including serotonin, dopamine, and norepinephrine is known to contribute to its etiology 4-6 , and the regulation of synaptic function through monoamine neurotransmitters serves as the primary approach to treat patients with depressive disorder 7,8. In addition, malfunctions of neuronal networks, such as an impaired balance between excitatory and inhibitory inputs, modulate emotional states, and previous studies suggest that glutamatergic and GABAergic systems are impaired in patients with depression 2,9,10. Furthermore, altered GABAergic inhibitory function induced by a change in the expression levels of GABAergic receptors also disrupts emotional processes in animal models of depressive disorders 9-14. Although the monoamine theory plays a major role in understanding the pathogenesis of depression, how the monoamine-independent changes in molecular and synaptic functions of neural networks contribute to depressive disorders remains largely elusive. The medial prefrontal cortex (mPFC) underlies the executive control of animal behavior 15,16 , and structural and functional changes in the mPFC, such as synaptic transmission and altered protein expression levels, are implicated in depression-related behaviors in animal models 15-18. For example, the deletion of the N-methyl-D-aspartic

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“…Hyperglycemia was induced immobilizing stress in the rabbits during 15 days (3 h daily) [22, 23]. They were roughly fixed on the board.…”

Section: Methodsmentioning

confidence: 99%

Antihyperglycemic and Antihyperlipidemic Activity of HydroponicStevia rebaudianaAqueous Extract in Hyperglycemia Induced by Immobilization Stress in Rabbits

Aghajanyan

Movsisyan

Trchоunian

2017

BioMed Research International

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Diabetes mellitus (DM) is a serious worldwide problem related to human hyperglycemia. Thus, herbal preparations with antihyperglycemic properties especially leaf extracts of hydroponic Stevia rebaudiana (SR) would be useful in hyperglycemia treatment. The antihyperglycemic potential of this medicinal plant grown using hydroponics methods has been evaluated. Significant reduction of some biochemical characteristics for sugars and fatty acids in blood, liver, and muscle especially fasting glucose levels, serum triglycerides, LDL-cholesterol, total cholesterol levels, and increased HDL-cholesterol ones was shown with SR aqueous extract treatment. Therefore, the aqueous extract of SR is suggested to have antihyperglycemic and antihyperlipidemic activity and to restore liver and muscle glycogen levels (hepatoprotective effects) in hyperglycemia induced by immobilization stress in rabbits and might be recommended for treatment of DM (hyperglycemia).

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Blood glucose regulation mechanism in depressive disorder animal model during hyperglycemic states

Cited by 12 publications

References 29 publications

Antidiabetic drug glyburide modulates depressive-like behavior comorbid with insulin resistance

Antidiabetic drug glyburide modulates depressive-like behavior comorbid with insulin resistance

Elevated O-GlcNAcylation induces an antidepressant-like phenotype and decreased inhibitory transmission in medial prefrontal cortex

Antihyperglycemic and Antihyperlipidemic Activity of HydroponicStevia rebaudianaAqueous Extract in Hyperglycemia Induced by Immobilization Stress in Rabbits

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