Abstract
Objective: The experiment aimed to find out the effectiveness of Zileuton, a 5-LOX inhibitor on depressive behavior and neuroinflammation in vivo.
 Method: Male ICR mice (25-30g) randomly distributed Veh+Veh, CRS+Vehicle, CRS+ZIL50, and CRS+ZIL100. Zileuton was orally given in the treatment groups for 21 days after 3 weeks of stress induce CRS model. Starting from the day 1, in CRS model, mice were immobilized 8 hr/day for consecutive 21 days to induce stress. After completing the drug administration, subjected the mice for behavioral tests, and then performed histopathological & Western Blotting.
 Result: Stress induces CRS model guide to the significant depressive-like behavior of the mice in behavioral tests which was united by adverse changes at the cellular/molecular level responsible for regulation of inflammatory and apoptotic processes. CRS triggered Microglial over activation in the DG of the hippocampus, which was successfully inhibited by Zileuton post-treatment at the dose of 100mg/kg than 50mg/kg. Level of TNF-α, IL- 1β, nuclear NF-κB p65, Bax, and cleaved Caspase-3 was high and Bcl-2 expression was low in the stress induce CRS -treated mice which were found to be opposite in the Zileuton (100mg/kg). However, the dose of 50mg/kg less to mimic the effects as exhibited more by the 100mg/kg dose of Zileuton.
 Conclusion: It can be concluded that selective 5-lipoxygenase inhibitor Zileuton can efficiently inhibit the depressive-like behavior/activity in CRS-induced depressive mouse model. The study is the first to show the role of 5-lipoxygenase enzyme in and Chronic Restraint Stress (CRS)-induced mice models of stress, anxiety or depression.
Highlights
The full mechanism of the pathogenesis of depression is not well known, depression is known to be associated with complex emotional disorders related to neurohormones pathway.Nowadays, the development of animal models provides an inner view to determine the mechanism responsible for the onset and inclined of the depressive disorder
The study is the first to show the role of 5-lipoxygenase enzyme in and Chronic Restraint Stress (CRS)-induced mice models of stress, anxiety or depression
We find out the activity of 5-LOX drug zileuton (50 mg/kg and 100 mg/kg) treatment on the tail suspension test (TST), forced swimming test (FST), novelty-suppressed feeding teat (NSFT), and open field test (OFT) in mice that repeatedly exposed to CORT
Summary
The full mechanism of the pathogenesis of depression is not well known, depression is known to be associated with complex emotional disorders related to neurohormones pathway.Nowadays, the development of animal models provides an inner view to determine the mechanism responsible for the onset and inclined of the depressive disorder. The full mechanism of the pathogenesis of depression is not well known, depression is known to be associated with complex emotional disorders related to neurohormones pathway. Chronic stress is a risk factor for emotional and psychiatry-related diseases such as depression [1]. Stress is considered among the critical issues for the growing up of mental disorders such as cognitive dysfunction and depression. Exposure to recurrent and longtime stress may tend to activate the hypothalamic-pituitary-adrenal axis (HPA) and sympathoadrenomedullary (SAM) system [2]. The level of corticosterone (CORT) is inclined by the activity of the HPA axis, which further affected cognitive function. Studies have exposed that chronic restraint stress (CRS) in the mice results in abnormal neurobehavioral activities such as anxiety, depression, and cognitive impairment. Restraint stress can induce oxidative/nitrite stress, pro-inflammatory cytokine release, increased expression of cyclooxygenase-2, and activation of activated NF-κB in different brain regions
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