The Neurochemical Changes Involved in Immobilization Stress-Induced Anxiety and Depression: Roles for Oxidative Stress and Neuroinflammation

2020 ◽  
Vol 14 (2) ◽  
pp. 133-149
Author(s):  
Kiarash Fekri ◽  
Alireza Mohajjel Nayebi ◽  
Saeed Sadigh-Eteghad ◽  
Fereshteh Farajdokht ◽  
Javad Mahmoudi
QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
I M Bahaaeldein ◽  
D A Aboubakr ◽  
N N Lasheen ◽  
N B E Soliman ◽  
M A Ahmed

Abstract Background Responses to stress could range from homeostatic variations to life-threatening effects depending on the type, timing and severity of the applied stimulus. Gender is accompanied by variations in oxidative stress, which causes the development of metabolic diseases. Under physiological conditions, females were found to be less susceptible to oxidative stress. Aim of work: This study was conducted to highlight the sex differences in the metabolic responses to chronic immobilization stress in rats, and to elucidate the possible underlying mechanisms. Materials and Methods Forty adult Wistar rats of both sexes; were randomly divided into 2 main groups: control group and stressed group, each of which was further subdivided into male and female groups. Stressed groups were exposed to chronic immobilization for 4 weeks. All rats were subjected to determination of body mass index, visceral fat weight, absolute and relative weights of liver and pancreas, plasma glucose, glucose uptake by diaphragm, glucose output by kidneys, lipid profile and plasma levels of insulin, leptin and sex hormones, malodialdehyde (MDA), total antioxidant capacity (TAC) and nitrite. HOMA-B and HOMA-IR were calculated. Also, caspase 3 was assessed in pancreas by immunohistochemistry. Results Stressed male rats showed lower BMI, higher relative liver weight, dyslipidemia, fasting hyperglycemia, higher glucose output by kidneys, lower glucose uptake by diaphragm, HOMA-B and plasma levels of insulin, testosterone and TAC and higher plasma estrogen and MDA levels compared to the control male group. Compared to the control female group, stressed female rate exhibited hyperglycemia, hypoinsulinemia, dyslipidemia, oxidative stress, higher plasma sex hormones. Compared to stressed male rats, stressed female group showed significantly higher BMI percentage change and plasma levels of TAC, estrogen and testosterone, but significantly lower absolute liver weight, glucose output by the kidneys, plasma levels of total cholesterol and triglycerides, and atherogenic index. Conclusion Chronic immobilization stress imposes greater hyperglycemic and hyperlipidemic status in males than in females. The altered sex hormonal pattern and lowered antioxidant defences could be contributory mechanisms


2020 ◽  
Vol 105 (4) ◽  
pp. 707-720 ◽  
Author(s):  
Javid Ghazizadeh ◽  
Sanaz Hamedeyazdan ◽  
Mohammadali Torbati ◽  
Fereshteh Farajdokht ◽  
Ali Fakhari ◽  
...  

2020 ◽  
Author(s):  
Junqiang Yan ◽  
Jiarui Huang ◽  
Jiannan Wu ◽  
Anran Liu ◽  
Mengmeng Shen ◽  
...  

Abstract Background Parkinson’s disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic neurons. It is characterized by static tremors, stiffness, slow movements, and gait disturbances, but it is also accompanied by anxiety and depression. Our previous study showed that statins, especially atorvastatin, could reduce the risk of PD, but the mechanism is still unclear. Results In this paper, we used an animal model of PD in which depression was determined by a tail suspension test, followed by an elevated plus-maze test to determine anxiety levels, and muscle status was measured by a rotarod test. We found that atorvastatin can increase muscle capacity and the coordination of movement and improved anxiety and depression,which mechanism may be related to decrease the expression of α-synuclein Ser129 and NADPH oxidase 2 (NOX2), and increase the protein expression of LC-3II/LC3-I, and promote autophagy flow. To further confirm that atorvastatin protection was achieved by inhibiting NOX2, we injected the midbrain substratum with NOX2 shRNA (M) lentivirus and found that silent NOX2 produced the same effect as atorvastatin. Further research found that atorvastatin could reduce MPTP-induced oxidative stress damage by increasing Nrf2, NQO-1 and HO-1, while inhibiting NOX2 decreased the antioxidative stress effect of atorvastatin. Conclusions: Our results suggest that atorvastatin can improve muscle capacity, anxiety and depression by inhibiting NOX2, which may be related to NOX2-mediated oxidative stress and autophagy in dopaminergic neurons. Atorvastatin may be identified as a drug that can effectively improve behavioral disorders in PD mice. NOX2 may be a potential gene target for new drug development in PD.


2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Dehua Liao ◽  
Daxiong Xiang ◽  
Ruili Dang ◽  
Pengfei Xu ◽  
Jiemin Wang ◽  
...  

Doxorubicin (DOX) is a broad-spectrum antitumor drug while its use is limited due to its neurobiological side effects associated with depression. We investigated the neuroprotective efficacy of dl-3-n-butylphthalide (dl-NBP) against DOX-induced anxiety- and depression-like behaviors in rats. dl-NBP was given (30 mg/kg) daily by gavage over three weeks starting seven days before DOX administration. Elevated plus maze (EPM) test, forced swimming test (FST), and sucrose preference test (SPT) were performed to assess anxiety- and depression-like behaviors. Our study showed that the supplementation of dl-NBP significantly mitigated the behavioral changes induced by DOX. To further explore the mechanism of neuroprotection induced by dl-NBP, several biomarkers including oxidative stress markers, endoplasmic reticulum (ER) stress markers, and neuroinflammatory cytokines in the hippocampus were quantified. The results showed that dl-NBP treatment alleviated DOX-induced neural apoptosis. Meanwhile, DOX-induced oxidative stress and ER stress in the hippocampus were significantly ameliorated in dl-NBP pretreatment group. Our study found that dl-NBP alleviated the upregulation of malondialdehyde (MDA), nitric oxide (NO), CHOP, glucose-regulated protein 78 kD (GRP-78), and caspase-12 and increased the levels of reduced glutathione (GSH) and activities of catalase (CAT), glutathione reductase (GR), and glutathione peroxidase (GPx) in the hippocampus of rats exposed to DOX. Additionally, the gene expression of interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-alpha (TNF-α) and protein levels of inducible nitric oxide synthase (iNOS) were significantly increased in DOX-treated group, whereas DOX-induced neuroinflammation was significantly attenuated in dl-NBP supplementation group. In conclusion, dl-NBP could alleviate DOX-induced anxiety- and depression-like behaviors via attenuating oxidative stress, ER stress, inflammatory reaction, and neural apoptosis, providing a basis as a therapeutic potential against DOX-induced neurotoxicity.


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