Imipramine treatment reverses depressive‐like behavior in alloxan‐diabetic rats

Ceretta, Luciane Bisognin; Réus, Gislaine Z.; Stringari, Roberto B.; Ribeiro, Karine F.; Zappellini, Giovanni; Aguiar, Bianca Wollenhaupt de; Pfaffenseller, Bianca; Lersh, Camila; Kapczinski, Flávio; Quevedo, Joao L De

doi:10.1002/dmrr.1285

Cited by 32 publications

(21 citation statements)

References 66 publications

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“…It is important to note that during the formation of memories the activation of specific receptors and of several molecular cascades is required to convert extracellular signals that lead to changes in neuronal connectivity [34], which were probably not altered in the brains of alloxan-induced diabetic rats. For example, we recently demonstrated that brain-derived neurotrophic factor (BDNF) levels did not alter in the hippocampus from alloxan-induced diabetic rats [35]. BDNF is a neurotrophin which has an important role in hippocampal-dependent forms of memory [36].…”

Section: Discussionmentioning

confidence: 99%

Increased Oxidative Stress and Imbalance in Antioxidant Enzymes in the Brains of Alloxan-Induced Diabetic Rats

Ceretta

Réus

Abelaira

et al. 2012

Experimental Diabetes Research

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Diabetes Mellitus (DM) is associated with pathological changes in the central nervous system (SNC) as well as alterations in oxidative stress. Thus, the main objective of this study was to evaluate the effects of the animal model of diabetes induced by alloxan on memory and oxidative stress. Diabetes was induced in Wistar rats by using a single injection of alloxan (150 mg/kg), and fifteen days after induction, the rats memory was evaluated through the use of the object recognition task. The oxidative stress parameters and the activity of antioxidant enzymes, superoxide dismutase (SOD), and catalase (CAT) were measured in the rat brain. The results showed that diabetic rats did not have alterations in their recognition memory. However, the results did show that diabetic rats had increases in the levels of superoxide in the prefrontal cortex, and in thiobarbituric acid reactive species (TBARS) production in the prefrontal cortex and in the amygdala in submitochondrial particles. Also, there was an increase in protein oxidation in the hippocampus and striatum, and in TBARS oxidation in the striatum and amygdala. The SOD activity was decreased in diabetic rats in the striatum and amygdala. However, the CAT activity was increased in the hippocampus taken from diabetic rats. In conclusion, our findings illustrate that the animal model of diabetes induced by alloxan did not cause alterations in the animals' recognition memory, but it produced oxidants and an imbalance between SOD and CAT activities, which could contribute to the pathophysiology of diabetes.

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Section: Discussionmentioning

confidence: 99%

Increased Oxidative Stress and Imbalance in Antioxidant Enzymes in the Brains of Alloxan-Induced Diabetic Rats

Ceretta

Réus

Abelaira

et al. 2012

Experimental Diabetes Research

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“…The previous studies have shown that diabetic animals presented higher depressive-like behavior in FST [28]. STZ diabetic rats showed decreased exploratory activity in OFT with a significant increase in immobility time in FST [29].…”

Section: Discussionmentioning

confidence: 83%

Biochemical Studies of Hippocampal Gene Expression of Brain-Derived Neurotropic Factor and Toll-Like Receptor-4 in Diabetic Rats Exposed to Chronic Stress: Effects of Antidepressant Drugs

Aboul‐Fotouh

Hassan

Habib

et al. 2018

Asian J Pharm Clin Res

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Objective: Depression and diabetes are closely associated in a reciprocal manner, leading to significant morbidity and mortality with an evidence of a pro-inflammatory state underlying pathophysiology of both diseases. Unfortunately, little information is available about the effects of antidepressant drugs on hippocampal brain-derived neurotrophic factor (BDNF) and toll-like receptor-4 (TLR-4) expression in diabetes. Methods:We investigated the effect of chronic administration of fluoxetine (FLU) and imipramine (IMIP) on behavioral, metabolic, and inflammatory abnormalities in diabetic and non-diabetic rats exposed to chronic restraint stress (CRS).Results: Both diabetes and CRS induced depressive-like behavior which was more prominent in diabetic/depressed rats; this was reversed by chronic treatment with FLU and IMIP. Diabetic and non-diabetic rats exposed to CRS showed a significant increase in hippocampal expression of TLR-4 and pro-inflammatory cytokines alongside a decrease in BDNF expression. FLU and IMIP ameliorated these inflammatory abnormalities. Conclusion:Diabetes mellitus (DM) and chronic stress induced a depressive-like behavior associated with an increase in hippocampal expression of TLR-4, tumor necrosis factor-α, and interleukin-1ß with a significant correlation to decreased BDNF expression. FLU and IMIP showed comparable effects regards the improvement of depressive and inflammatory abnormalities associated with DM.

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“…[36] Alloxan-induced diabetes in mice exhibited increased duration of immobility in FST and TST, which is consistent with the results obtained in previous studies. [7] It revealed the development of depressive episodes as a consequence of diabetes in mice. [36,37] EAV effectively reversed diabetes-induced behavioural despair effects in FST and TST without altering the generalised motor performance and the effect was similar to that of the anti-depressant drug, ESC.…”

Section: Discussionmentioning

confidence: 98%

“…[6] Earlier studies have demonstrated the consequences of depression in alloxan-induced diabetes such as decrease in duration of immobility in forced swim test (FST) and prolonged desperate behaviour and decreased exploratory activity in open field test. [7,8] Reports have shown that alloxan-induced diabetes results in increased brain monoamine oxidase (MAO) activity. [9,10] Furthermore, alloxan-induced diabetes is known to increase oxidative stress in the brain resulting in altered neuronal activity.…”

Section: Introductionmentioning

confidence: 99%

Effects of Adhatoda vasica leaf extract in depression co-morbid with alloxan-induced diabetes in mice

Gupta¹,

Mahesh²,

Kurhe³

2014

Int J Green Pharm

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Context: Increased neuronal oxidative stress as a consequence of diabetes may result in neuropsychological complications such as depression. Depression co-morbid with diabetes further hampers the quality life years in diabetic patients. Aim: Thus, the present study was aimed at investigating the effects of Adhatoda vasica leaf extract (EAV), as a natural remedy, in alloxan-induced diabetes and co-morbid depression in mice. Materials and Methods: Experimentally, mice were rendered diabetic with a single dose of alloxan of 200 mg/kg, intraperitoneally (i.p.). After 3 weeks of having chronic diabetic state, mice were given EAV (100-400 mg/kg, orally)/ vehicle/standard control (escitalopram, ESC; 10 mg/kg, orally) for 7 days. After dosing, anti-diabetic effect was detected by the fasted blood glucose levels and anti-depressant effect was evaluated by behavioural despair tests, followed by monoamine oxidase (MAO) activity and oxidative stress analysis. Results and Discussion: EAV treatment effectively reduced the elevated blood glucose levels and reversed co-morbid depressive behaviour. Furthermore, EAV inhibited diabetes induced increased oxidative stress and MAO activity in the brain. Thus, EAV demonstrated the potential protective action against oxidative stress and revealed monoamine modulatory activity in the brain, which may contribute to its anti-depressant effect. Conclusion: This work demonstrates the efficacious effect of EAV in reversing the depression co-morbid with alloxan-induced diabetes in mice.

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Imipramine treatment reverses depressive‐like behavior in alloxan‐diabetic rats

Abstract: In conclusion, this study demonstartes a link between diabetes and depression in rats and that imipramine exerted antidepressant effects in diabetic animals.

Cited by 32 publications

References 66 publications

Increased Oxidative Stress and Imbalance in Antioxidant Enzymes in the Brains of Alloxan-Induced Diabetic Rats

Increased Oxidative Stress and Imbalance in Antioxidant Enzymes in the Brains of Alloxan-Induced Diabetic Rats

Biochemical Studies of Hippocampal Gene Expression of Brain-Derived Neurotropic Factor and Toll-Like Receptor-4 in Diabetic Rats Exposed to Chronic Stress: Effects of Antidepressant Drugs

Effects of Adhatoda vasica leaf extract in depression co-morbid with alloxan-induced diabetes in mice

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