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Antidepressant, Anxiolytic and Neuroprotective Activities of Two Zinc Compounds in Diabetic Rats.

ABSTRACT: Behavioral disorders affect most diabetic patients and Zinc (Zn) has been used among adjuvant therapies for involvement in the etiology of depression and anxiety, however, the results are still controversial. The objective of this study was to compare the antidepressant, anxiolytic and neuroprotective activity of the supplementation of two Zn compounds in an animal model of Diabetes Mellitus type 1 (DM1). Thirty-eight (38) adult rats were randomized into four groups: Control (C; n = 8); Diabetic (D; n = 10); Diabetic Zn Sulfate Supplement (DSZ; n = 10) and Diabetic Zn Gluconate Supplement (DGZ; n = 10). The DSZ group received Zn sulfate supplementation and the DGZ group received Zn gluconate supplementation at a dose of 15 mg/kg for 4 weeks. Data (mean ±SEM) were analyzed by the Mann-Whitney test with a significance level of p < 0.05. The results indicate that Zn gluconate supplementation in diabetic animals presented an antidepressant effect demonstrated through the results obtained in the Forced Swim Test, and neuroprotective effect by attenuating alterations in the cerebral cortex; while Zn sulfate supplementation in diabetic animals showed an anxiolytic effect demonstrated by the results obtained in the open field test and the elevated plus maze test. Considering the set of results, supplementation with both zinc compounds showed neurobehavioral benefits in diabetic animals with different effects depending on the type of anion associated with Zn.

SUBMITTER: Cavalcanti CL

PROVIDER: S-EPMC6985554 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Antidepressant, Anxiolytic and Neuroprotective Activities of Two Zinc Compounds in Diabetic Rats.

Cavalcanti Christiane Leite CL Gonçalves Maria Conceição Rodrigues MCR Alves Adriano Francisco AF de Araújo Emmanuel Veríssimo EV Carvalho Jader Luciano P JLP Lins Priscilla Paulo PP Alves Raquel Coutinho RC Soares Naís Lira NL Pordeus Liana Clebia Morais LCM Aquino Jailane Souza JS

Frontiers in neuroscience 20200121

Behavioral disorders affect most diabetic patients and Zinc (Zn) has been used among adjuvant therapies for involvement in the etiology of depression and anxiety, however, the results are still controversial. The objective of this study was to compare the antidepressant, anxiolytic and neuroprotective activity of the supplementation of two Zn compounds in an animal model of Diabetes Mellitus type 1 (DM1). Thirty-eight (38) adult rats were randomized into four groups: Control (C; <i>n</i> = 8); D ...[more]

PMID: 32038128

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Project description:Clinical and preclinical studies have implicated glial anomalies in major depression. Conversely, evidence suggests that the activity of antidepressant drugs is based, at least in part, on their ability to stimulate density and/or activity of astrocytes, a major glial cell population. Despite this recent evidence, little is known about the mechanism(s) by which astrocytes regulate emotionality. Glial cells communicate with each other through gap junction channels (GJCs), while they can also directly interact with neurons by releasing gliotransmitters in the extracellular compartment via an hemichannels (HCs)-dependent process. Both GJCs and HCs are formed by two main protein subunits: connexins (Cx) 30 and 43 (Cx30 and Cx43). Here we investigate the role of hippocampal Cx43 in the regulation of depression-like symptoms using genetic and pharmacological approaches. The first aim of this study was to evaluate the impact of the constitutive knock-down of Cx43 on a set of behaviors known to be affected in depression. Conversely, the expression of Cx43 was assessed in the hippocampus of mice subjected to prolonged corticosterone (CORT) exposure, given either alone or in combination with an antidepressant drug, the selective serotonin reuptake inhibitor fluoxetine. Our results indicate that the constitutive deficiency of Cx43 resulted in the expression of some characteristic hallmarks of antidepressant-/anxiolytic-like behavioral activities along with an improvement of cognitive performances. Moreover, in a new cohort of wild-type mice, we showed that CORT exposure elicited anxiety and depression-like abnormalities that were reversed by chronic administration of fluoxetine. Remarkably, CORT also increased hippocampal amounts of phosphorylated form of Cx43 whereas fluoxetine treatment normalized this parameter. From these results, we envision that antidepressant drugs may exert their therapeutic activity by decreasing the expression and/or activity of Cx43 resulting from a lower level of phosphorylation in the hippocampus.

Project description:IntroductionRecent studies have reported a strong relationship between diabetes and anxiety- and depression-like behaviors; however, there is a lack of information on the underlying pathophysiology. Alkaline Zamzam water (ZW), which is rich in several trace elements, has neuroprotective properties. This study aimed to investigate the anxiolytic and antidepressant effects of ZW against diabetes-induced behavioral changes and shed light on the possible underlying mechanisms.MethodsForty-eight rats were divided into four experimental groups (n = 12): group I (control group), group II (Zamzam water group), group III (diabetic group), and group IV (diabetic + Zamzam water group). Diabetes was induced by an intraperitoneal injection of 60 mg/kg streptozotocin (STZ). At the end of the experiment, the forced swimming test (FST) was used to assess depression-like effects. The elevated plus maze test (EPMT) and open field test (OFT) were performed to evaluate anxiety-like behavior. Blood levels of the hypothalamic-pituitary-adrenal (HPA) axis were measured, and prefrontal cortex and hippocampal tissue samples were removed for histological, immunohistochemical, ELISA, and Q-PCR analyses.ResultsZW significantly decreased the immobility time in the FST, indicating an antidepressant effect (p < 0.001). Additionally, ZW significantly improved the OFT and open field entry (OFE) percentages in the EPMT, increasing center crossing and decreasing grooming and fecal boli in the OFT. This indicated an anxiolytic-like effect in diabetic rats with histological improvement. Interestingly, ZW significantly increased prefrontal cortical and hippocampal levels of antioxidant enzymes and the Nrf2/HO-1 pathway. It also modulated the HPA axis by increasing cortisol and corticotropin-releasing hormone (CRH) levels, with a decrease in ACTH and an increase in monoamine neurotransmitters. Furthermore, diabetic rats that received ZW showed a decrease in the inflammatory markers TNF-α and GFAP by immunohistochemistry and in the mRNA levels of NFκB, IL-1β, and IL6. In addition, ZW downregulated the expression of the BDNF/ERK2/CREP pathway.ConclusionOur results suggested a neuroprotective effect of ZW against diabetes-induced anxiety- and depression-like behaviors and explored the underlying mechanisms. These findings suggest a promising therapeutic strategy for patients with diabetes who experience anxiety and depression.

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Antidepressant, Anxiolytic and Neuroprotective Activities of Two Zinc Compounds in Diabetic Rats.

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Antidepressant, Anxiolytic and Neuroprotective Activities of Two Zinc Compounds in Diabetic Rats.

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