Increased oxidative stress in prefrontal cortex and hippocampus is related to depressive-like behavior in streptozotocin-diabetic rats

Morais, Helen de; Souza, Camila Pasquini de; Silva, Luisa M. da; Ferreira, Daniele Masterson Tavares Pereira; Werner, Maria Fernanda de Paula; Andreatini, Roberto; Cunha, Joice Maria da; Zanoveli, Janaína Menezes

doi:10.1016/j.bbr.2013.10.011

Cited by 95 publications

(38 citation statements)

References 88 publications

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“…In agreement with prior studies (Ates et al 2007;de Morais et al 2014), this study shows that STZ-induced diabetic rats have increased brain levels of MDA (which is an end-product of lipid peroxidation), and reduced brain levels of non-enzymatic endogenous anti-oxidants, namely GSH, owing to increased levels of ROS and lipid peroxides, when compared with the normal rats. This suggests that STZ-induced oxidative stress resulting from chronic hyperglycaemia may account for the depressive behavior in diabetic rats.…”

Section: Discussionsupporting

confidence: 91%

Anti-depressant effect of hesperidin in diabetic rats

El-Marasy

Abdallah

El‐Shenawy

et al. 2014

Can. J. Physiol. Pharmacol.

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This study aimed to investigate the anti-depressant effect of hesperidin (Hsp) in streptozotocin (STZ)-induced diabetic rats. Additionally, the effect of Hsp on hyperglycaemia, oxidative stress, inflammation, brain-derived neurotrophic factor (BDNF), and brain monoamines in diabetic rats was also assessed. The Wistar rats in the experimental groups were rendered hyperglycaemic with a single dose of STZ (52.5 mg·(kg body mass)(-1), by intraperitoneal injection). The normal group received the vehicle only. Hyperglycaemic rats were treated with Hsp (25.0, 50.0, or 100.0 mg·(kg body mass)(-1)·day(-1), per oral) and fluoxetine (Flu) (5.0 mg·(kg body mass)(-1)·day(-1), per oral) 48 h after the STZ injection, for 21 consecutive days. The normal and STZ control groups received the vehicle (distilled water). Behavioral and biochemical parameters were then assessed. When Hsp was administered to the STZ-treated rats, this reversed the STZ-induced increase in immobility duration in the forced swimming test (FST) and attenuated hyperglycaemia, decreased malondialdehyde (MDA), increased reduced glutathione (GSH) decreased interleukin-6 (IL-6), and increased BDNF levels in the brain. Treatment with Hsp attenuated STZ-induced neurochemical alterations, as indicated by increased levels of monoamines in the brain, namely, norepinephrine (NE), dopamine (DA), and serotonin (5-hydroxytryptamine; 5-HT). All of these effects of Hsp were similar to those observed with the established anti-depressant Flu. This study shows that Hsp exerted anti-depressant effect in diabetic rats, which may have been partly mediated by its amelioration of hyperglycaemia as well as its anti-oxidant and anti-inflammatory activities, the enhancement of neurogenesis, and changes in the levels of monoamines in the brain.

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Section: Discussionsupporting

confidence: 91%

Anti-depressant effect of hesperidin in diabetic rats

El-Marasy

Abdallah

El‐Shenawy

et al. 2014

Can. J. Physiol. Pharmacol.

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“…We observed no differences in the immobility behaviour between T2DM and non‐diabetic animals submitted to the FST. These results differ from those of studies using animal model for T1DM, in which significant differences in immobility time between diabetic and non‐diabetic rats submitted to the FST were observed . This model is characterized by severe hyperglycaemia due to the total destruction of pancreatic cells .…”

Section: Discussioncontrasting

confidence: 93%

Antidepressant‐like Effect of Insulin in Streptozotocin‐induced Type 2 Diabetes Mellitus Rats

Sestile

Maraschin

Rangel

et al. 2016

Basic Clin Pharma Tox

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This study evaluated the antidepressant-like effect of insulin compared to sertraline and a combination of insulin and sertraline in streptozotocin (STZ)-induced type 2 diabetes mellitus (T2DM) rats submitted to the forced swim test (FST). Male Wistar rats were daily treated for 21 days with insulin (1 or 2 IU/kg, i.p.), with the selective serotonin reuptake inhibitor (SSRI), sertraline (10 mg/kg, i.p.), or with a combination of insulin (1 or 2 IU/kg, i.p.) and sertraline (10 mg/kg, i.p.) and submitted to the FST. We also evaluated the water and food intake, urine volume and weight gain of the rats. Rats treated with STZ showed impaired glucose tolerance. Chronic treatment with sertraline showed an antidepressant-like effect in non-diabetic and diabetic rats. Furthermore, sertraline promoted lower weight gain in diabetic rats. Insulin reduced the immobility behaviour in T2DM rats with impaired glucose tolerance. In conclusion, our results showed that insulin has an antidepressant-like effect comparable to that of sertraline. Sertraline is effective as an antidepressant and reduces weight gain, which reinforces its superiority over other SSRIs in the treatment of major depression disorder in patients with T2DM.Global estimates indicate that approximately 382 million people worldwide have diabetes, 316 million have impaired glucose tolerance and 90% of patients are diagnosed with type 2 diabetes mellitus (T2DM) [1]. Major depressive disorder (MDD) is the most common psychiatric comorbidity diagnose in patients with T2DM [1], with a global prevalence ranging from 11% to 30% [2].MDD amplifies the perception of diabetes symptoms [3], worsens glycaemic control and increases the complications of diabetes such as retinopathy, neuropathy, sexual dysfunction and macrovascular complications [4]. The treatment of MDD is necessary to improve the quality of life and to increase the adherence to glycaemic control therapies in patients with diabetes. Currently, selective serotonin reuptake inhibitors (5-HT, SSRIs) are the main therapeutic option in the treatment of MDD in patients with or without diabetes due to low incidence of adverse effects compared to tricyclic antidepressants, such as anticholinergic effects, on the cardiovascular system and glycaemic control [5,6].Although the mechanisms involved in the relationship between T2DM and MDD are not yet fully understood, studies show the involvement of insulin on different cognitive brain functions such as learning and memory [7]. Insulin is a peptide hormone effective in the control and reduction of blood glucose and is widely used in the treatment of diabetes [8].Insulin also participates in the neurobiological processes related to hunger, reproduction and cognition by modulating neurotransmitter hormones such as 5-HT [9][10][11][12]. Furthermore, other studies show that the increase in 5-HT in the hypothalamus of rats, obtained by the administration of a release and inhibitor of 5-HT reuptake agent, dexfenfluramine, produces an immediate increase in insulin level...

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“…Glutathione in particular plays a major role in the redox process (Schafer and Buettner, 2001) and affects the brain by directly detoxifying drugs, ROS, and electrophilic xenobiotics, being a source of cysteine, promoting neurodevelopment and enhancing excitatory glutamatergic neurotransmission (Kohr et al, 1994;Meister, 1988;Shi et al, 2000). Oxidative stress and inflammation contribute notably to major depression (de Morais et al, 2014;Rawdin et al, 2013). In a meta-analysis based on 4908 subjects, depression was associated with high oxidative stress status and with an imbalance towards oxidative markers rather than anti-oxidants (Palta et al, 2014).…”

Section: Neuroinflammation and Oxidative Stressmentioning

confidence: 99%

The role of pro-inflammatory cytokines in neuroinflammation, neurogenesis and the neuroendocrine system in major depression

Kim

Lee

Myint

et al. 2016

Progress in Neuro-Psychopharmacology and Biological Psychiatry

497

294

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Cytokines are pleiotropic molecules with important roles in inflammatory responses. Pro-inflammatory cytokines and neuroinflammation are important not only in inflammatory responses but also in neurogenesis and neuroprotection. Sustained stress and the subsequent release of pro-inflammatory cytokines lead to chronic neuroinflammation, which contributes to depression. Hippocampal glucocorticoid receptors (GRs) and the associated hypothalamus-pituitary-adrenal (HPA) axis have close interactions with pro-inflammatory cytokines and neuroinflammation. Elevated pro-inflammatory cytokine levels and GR functional resistance are among the most widely investigated factors in the pathophysiology of depression. These two major components create a vicious cycle. In brief, chronic neuroinflammation inhibits GR function, which in turn exacerbates pro-inflammatory cytokine activity and aggravates chronic neuroinflammation. On the other hand, neuroinflammation causes an imbalance between oxidative stress and the anti-oxidant system, which is also associated with depression. Although current evidence strongly suggests that cytokines and GRs have important roles in depression, they are essential components of a whole system of inflammatory and endocrine interactions, rather than playing independent parts. Despite the evidence that a dysfunctional immune and endocrine system contributes to the pathophysiology of depression, much research remains to be undertaken to clarify the cause and effect relationship between depression and neuroinflammation.

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Increased oxidative stress in prefrontal cortex and hippocampus is related to depressive-like behavior in streptozotocin-diabetic rats

Cited by 95 publications

References 88 publications

Anti-depressant effect of hesperidin in diabetic rats

Anti-depressant effect of hesperidin in diabetic rats

Antidepressant‐like Effect of Insulin in Streptozotocin‐induced Type 2 Diabetes Mellitus Rats

The role of pro-inflammatory cytokines in neuroinflammation, neurogenesis and the neuroendocrine system in major depression

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