Minocycline protects against oxidative damage and alters energy metabolism parameters in the brain of rats subjected to chronic mild stress

ObjectivesThe present study was aimed at evaluating the effects of the administration of β-carboline harmine on behaviour and citrate synthase activity in the brain of rats exposed to chronic mild stress (CMS) procedure.MethodsTo this aim, after 40 days of exposure to CMS procedure, rats were treated with harmine (15 mg/kg/day) for 7 days, then memory, anhedonia and citrate synthase activity were assessed.ResultOur findings demonstrated that stressed rats treated with saline increased the sucrose intake, and the stressed rats treated with harmine reversed this effect. Neither stress nor harmine treatment altered memory performance in rats. In addition, chronic stressful situations induced increase in citrate synthase activity in the prefrontal cortex, but not in the hippocampus and striatum. Treatment with harmine reversed the increase in citrate synthase activity in the prefrontal cortex.ConclusionThese findings support the hypothesis that harmine could be involved in controlling the energy metabolism.

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Modulation of the Nuclear Factor (Erythroid 2-Derived)-Like 2 Pathway by Antidepressants In Rats

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.1951 ◽

2016 ◽

Vol 33 (S1) ◽

pp. S527-S527

Author(s):

D. Martín Hernández ◽

Á.G. Bris ◽

K.S. MacDowell ◽

A. Sayd ◽

D. Azpiazu ◽

...

Keyword(s):

Oxidative Damage ◽

Wistar Rats ◽

Nitrosative Stress ◽

Chronic Mild Stress ◽

Mild Stress ◽

Nuclear Factor ◽

Nrf2 Pathway ◽

Antidepressant Treatments ◽

Male Wistar Rats ◽

Competing Interest

IntroductionPatients with major depression who are otherwise medically healthy have activated inflammatory pathways. It has been described that depression is not only escorted by inflammation but also by induction of multiple oxidative/nitrosative stress pathways. Nevertheless, there are finely regulated mechanisms involved in preserving cells from damage, such as the nuclear factor Nrf2.AimsTo explore in a depression-like model the Nrf2 pathway in the prefrontal cortex (PFC) and the hippocampus of rats and to analyze which classic antidepressants affect the antioxidant activity of the Nrf2 pathway.MethodsMale Wistar rats were exposed to chronic mild stress (CMS) and some of them were treated with desipramine, escitalopram or duloxetine. We studied the expression in the PFC and hippocampus of upstream and downstream elements of the Nrf2 pathway and the oxidative damage induced by the CMS.ResultsAfter exposure to a CMS protocol, in the PFC, there is an inhibition of upstream and downstream elements of the Nrf2 pathway. Moreover, antidepressant treatments, particularly desipramine and duloxetine, are able to recover some of these elements and to reduce the oxidative damage induced by the depression model. In the hippocampus however, Nrf2 pathways are not that affected and antidepressants do not have many actions.ConclusionsNrf2 pathway is differentially regulated by antidepressants in the PFC and hippocampus. The Nrf2 pathway is involved in the oxidative/nitrosative damage detected in the PFC after CMS exposure. However, it seems that Nrf2 is not very involved in the effects caused by the CMS in the hippocampus.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Chinese medicine Banxia-houpu decoction regulates c-fos expression in the brain regions in chronic mild stress model in rats

Phytotherapy Research ◽

10.1002/ptr.1391 ◽

2004 ◽

Vol 18 (3) ◽

pp. 200-203 ◽

Cited By ~ 9

Author(s):

Weiyun Zhang ◽

Jianmei Li ◽

Jixiao Zhu ◽

Zhenqiu Shi ◽

Yong Wang ◽

...

Keyword(s):

Chinese Medicine ◽

Chronic Mild Stress ◽

Brain Regions ◽

Mild Stress ◽

Stress Model ◽

Fos Expression ◽

The Brain

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Microstructural and Metabolic Recovery of Anhedonic Rat Brains: An In Vivo Diffusion MRI and 1H-MRS Approach

Data ◽

10.3390/data3030029 ◽

2018 ◽

Vol 3 (3) ◽

pp. 29 ◽

Cited By ~ 2

Author(s):

Ahmad Khan ◽

Sune Jespersen ◽

Ove Wiborg ◽

Christopher Kroenke ◽

Brian Hansen

Keyword(s):

Diffusion Mri ◽

Imaging System ◽

Chronic Mild Stress ◽

Ventral Hippocampus ◽

Control Group ◽

Mild Stress ◽

1H Mrs ◽

Unpredictable Chronic Mild Stress ◽

The Brain

This article presents longitudinal 1H-MR Spectroscopy (1H-MRS) data from ventral hippocampus and in vivo diffusion MRI (dMRI) data of the brain from control and anhedonic rats. The 1H-MRS and dMRI data were acquired using a 9.4 T preclinical imaging system. Before MRI experiments, animals were exposed to unpredictable chronic mild stress exposure for eight weeks and on the basis of a sucrose consumption test were identified as anhedonic and resilient. An age-matched group of animals, unexposed to the unpredictable chronic mild stress paradigm was considered as control. Data was acquired at the age of 18, 20 and 25 weeks in the anhedonic group and at the age of 18 and 22 weeks in the control group. This multimodal MRI data provides metabolic information of ventral hippocampus and dMRI based microstructural parameters of the brain.

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The Changes of Expression and Methylation of Genes Involved in Oxidative Stress in Course of Chronic Mild Stress and Antidepressant Therapy with Agomelatine

Genes ◽

10.3390/genes11060644 ◽

2020 ◽

Vol 11 (6) ◽

pp. 644

Author(s):

Paulina Wigner ◽

Ewelina Synowiec ◽

Paweł Jóźwiak ◽

Piotr Czarny ◽

Michał Bijak ◽

...

Keyword(s):

Oxidative Stress ◽

Nitrosative Stress ◽

Mononuclear Cells ◽

Methylation Status ◽

Chronic Mild Stress ◽

Mild Stress ◽

Oxidative And Nitrosative Stress ◽

Peripheral Blood Mononuclear ◽

Taqman Gene Expression Assay ◽

The Brain

Preclinical studies conducted so far suggest that oxidative stress processes may be associated with the mechanism of depression development. This study shows the effects of chronic administration of agomelatine on expression and the methylation status of Sod1, Sod2, Gpx1, Gpx4, Cat, Nos1, and Nos2 in the brain stricture and blood in the chronic mild stress (CMS) animal model of depression. The animals were exposed to the CMS procedure and treatment with agomelatine (10 mg/kg/day, IP) for five weeks and then were sacrificed. TaqMan Gene Expression Assay, Western blot, and methylation-sensitive high-resolution melting techniques were used to evaluate mRNA and protein expression of the genes, and the methylation status of their promoters. Gpx1, Gpx4, and Sod2 expression in the PBMCs and Sod1 and Sod2 expression in the brain were reduced in the stressed group after agomelatine administration. CMS caused an increase in the methylation of the third Gpx4 promoter in peripheral blood mononuclear cells and Gpx1 promoter in the cerebral cortex. Additionally, stressed rats treated with agomelatine displayed a significantly lower Gpx4 level in the hypothalamus. The results confirm the hypothesis that the CMS procedure and agomelatine administration change the expression level and methylation status of the promoter region of genes involved in oxidative and nitrosative stress.

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Chronic mild stress leads to aberrant glucose energy metabolism in depressed Macaca fascicularis models

Psychoneuroendocrinology ◽

10.1016/j.psyneuen.2019.05.007 ◽

2019 ◽

Vol 107 ◽

pp. 59-69 ◽

Cited By ~ 10

Author(s):

Yinhua Qin ◽

XiaoFeng Jiang ◽

Wei Li ◽

Jie Li ◽

Tian Tian ◽

...

Keyword(s):

Energy Metabolism ◽

Macaca Fascicularis ◽

Chronic Mild Stress ◽

Mild Stress

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P.1.003 Inflammatory response in the brain of rats exposed to chronic mild stress

European Neuropsychopharmacology ◽

10.1016/s0924-977x(13)70005-1 ◽

2013 ◽

Vol 23 ◽

pp. S5-S6

Author(s):

C. Zecchillo ◽

F. Macchi ◽

R. Molteni ◽

G. Racagni ◽

M. Papp ◽

...

Keyword(s):

Inflammatory Response ◽

Chronic Mild Stress ◽

Mild Stress ◽

The Brain

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Cell type-specific in vivo expression of genes encoding signalling molecules in the brain in response to chronic mild stress and chronic treatment with fluoxetine

Psychopharmacology ◽

10.1007/s00213-015-3921-2 ◽

2015 ◽

Vol 232 (15) ◽

pp. 2827-2835 ◽

Cited By ~ 15

Author(s):

Lu Dong ◽

Baoman Li ◽

Alexei Verkhratsky ◽

Liang Peng

Keyword(s):

Chronic Treatment ◽

Chronic Mild Stress ◽

Mild Stress ◽

Cell Type ◽

Signalling Molecules ◽

Expression Of Genes ◽

Genes Encoding ◽

Cell Type Specific ◽

The Brain

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Haloperidol and aripiprazole impact on the BDNF and glucocorticoid receptor levels in the rat hippocampus and prefrontal cortex: effect of the chronic mild stress

Endocrine Regulations ◽

10.2478/enr-2021-0016 ◽

2021 ◽

Vol 55 (3) ◽

pp. 153-162

Author(s):

Jana Osacka ◽

Romana Koprdova ◽

Andrej Tillinger ◽

Zdenko Pirnik ◽

Alexander Kiss

Keyword(s):

Prefrontal Cortex ◽

Weight Gain ◽

Glucocorticoid Receptor ◽

Chronic Mild Stress ◽

Mild Stress ◽

Typical Antipsychotic ◽

Mrna Levels ◽

Frozen Sections ◽

Bdnf Mrna ◽

The Brain

Abstract Objective. Changes in the brain derived neurotrophic factor (BDNF) and glucocorticoid receptor (GR) expression in the prefrontal cortex (PFC) and hippocampus (HIP) are associated with psychiatric diseases and stress response. Chronic mild stress (CMS) may alter BDNF as well as GR levels in both the PFC and the HIP. The aim of the present study was to find out whether chronic treatment with a typical antipsychotic haloperidol (HAL) and an atypical antipsychotic aripiprazole (ARI) may modify the CMS effect on the BDNF and GR expression in the above-mentioned structures. Methods. The rats were exposed to CMS for 3 weeks and from the 7th day of CMS injected with vehicle (VEH), HAL (1 mg/kg) or ARI (10 mg/kg) for 4 weeks. BDNF and GR mRNA levels were established in the PFC and the HIP by Real Time PCR, whereas, PFC and HIP samples were obtained by punching them from 500 µm thick frozen sections. C-Fos immunoreactivity was analyzed in the PFC and the HIP on 30 µm thick paraformaldehyde fixed sections. Weight gain and corticosterone (CORT) levels were also measured. Results. The CMS and HAL suppressed the BDNF and GR mRNA levels in the PFC. In the HIP, CMS elevated BDNF mRNA levels that were suppressed by HAL and ARI treatments. The CMS decreased the c-Fos immunoreactivity in the PFC in both HAL- and ARI-treated animals. In the HIP, HAL increased the c-Fos immunoreactivity that was again diminished in animals exposed to CMS. Stressed animals gained markedly less weight until the 7th day of CMS, however, later their weight gain did not differ from the unstressed ones or was even higher in CMS+HAL group. Un-stressed HAL and ARI animals gained less weight than the VEH ones. Neither CMS nor HAL/ARI affected the plasma CORT levels. Conclusion. The present data indicate that HAL and ARI in the doses 1 mg/kg or 10 mg/kg, respectively, does not modify the effect of the CMS preconditioning on the BDNF and GR mRNA levels in the PFC or the HIP. However, HAL seems to modify the CMS effect on the HIP activation.

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