| With the scientific and technologic development, the increasingly competitive challenges-stress-are here and there in modern society. Stress has gradually become popular in people's life. Research shows that the stress response is actually a pro-inflammatory response, along with neuropsychiatric and other system disorders. In recent years, studies have shown that inflammation ties chronic mental disorders, and cytokines such as IL-1β and IL-6increased in the serum of patients with depression found in the study. In the human body, there exists a bidirectional communication between the central nervous system and the immune system. Cytokines, neurotransmitters, hormones and other chemical information of molecular exchange are the common signal. When the body is in stressful situations, the stress hormones secret to regulate and change the function of the immune system.Depression is a common mental disorder, which causes mental illness and suicide. Depression mainly manifests depressed emotion, mental retardation, the lack of interest in pleasure, despair, and severe cases, accompanied by suicidal tendencies. According to the literature reports, the incidence of depression is about10%, and50%-70%of suicide is related with depression. In the worldwide, the incidence of depression showing a rising trend, and accompanied by the development of a younger age. Speculated that, according to World Health Organization, in2020, the depression, the four major disease emerged as the world's No.2disease from all the world's major non-fatal disease, take a huge burden on it. Depression as more serious diseases of modern society, because of its high incidence, high-disability, a heavy burden on families and the community while also attracted great attention. Over the years, medical scientists are committed to research in the field of depression, important progress has been made. However, the pathogenesis of depression is very complex, and the pathogenesis of the different causes of depression may be different, so as yet the mechanism of depression is still not clear. Different to the usual understanding of depression, it is not a general emotional or psychological problem. Medical research shows that it is a clear biological basis of disease, is a psychological neuro-immune disorder. Research on depression, the depression of the inflammatory response doctrine in the development and prevention of depression has attracted much attention. The doctrine is based on depression in patients with immunological change. The main idea of this doctrine is that the activation of the immune system plays an important role in the pathogenesis of depression. Results from clinical and animal experiments have confirmed this idea.The importance of the biological medium of nitric oxide (NO) on the body's physiological role, especially the central nervous system caused widespread concern. As a freedom of gaseous molecules, it is also involved in the regulation of the nervous and immune systems. Studies suggest that NO play certain roles in the depression caused by stress. NO is an important immune quenched and tempered. In the field of depression, the role of NO has attracted the interest of researchers. However, study showed relatively poor, and even opposite result about the role of NO in depression.NO is catalyzed by nitric oxide synthase (NOS). According to the characteristics, NOS can be divided into three types, namely, nNOS (neuronal), iNOS in the (inducible) and eNOS (endothelial). nNOS and eNOS, also known as the structure type of cNOS, sustained expression of its activity is calcium dependent, for the physiological enzyme formation. iNOS is a non-calcium dependent, in the ground state does not work in the inflammatory cytokine induced a large number of generated, and the synthesis of NO compared with cNOS about1000times higher, presumably as a "pathological" enzyme formation. Under normal physiological conditions, nNOS is the main source of central NO; central glial cells produce large amounts of inflammatory factors in the inflammatory state, and activation of iNOS in it.About the relationship between iNOS and depression, studies have reported different, even the biphasic regulatory role of NO on the neurotransmitters, such as the biphasic effect of depression. Therefore, the role of NO in the pathogenesis of depression has yet to be confirmed. NO depression, NO and KP pathway and NO and the immune inflammatory response in several areas have people study and what kind of causal relationship between NO and stress and inflammatory depression. In particular, exist in the whole animal, the stress response and even, the stress causes the body immune inflammatory response or stress and the immune inflammatory response coexistence of NO which play a important role and in how it is the worth exploring.As previously reported that acute and chronic immune system activation play an important role in the occurrence and development of depression. This view is consistent with reports from other laboratories. Experiences and inflammatory mediators are fundamental in the provocation of major depressive disorders (MDD). We investigated the roles and mechanisms of iNOS in inflammatory depression. Based on the doctrine of the inflammatory response of depression, we hypothesized that acute and chronic stress caused acute and chronic immune system activation-induced depression may be closely related to NO and iNOS pathway, and it may play an important role in the process. We used unpredictable chronic mild stress (UCMS) and acute administration of low doses of endotoxin to simulate the immune inflammatory response as acute and chronic stress conditions, which aims to establish the animal inflammatory model of depression (this two models have been more mature and widely accepted). Depressive-like behaviors, iNOS pathway and neuron damage were observed in the present or absent of iNOS antagonist1400w. We used two mouse model of depressive-like state induced by UCMS and LPS. Depressive-like behaviors were evaluated with sucrose preference, locomotor activity and forced swim test. Immunohistochemistry was used to check the loss of Nissl bodies in cerebral cortex neurons. The levels of iNOS mRNA expression in the brain and nitrites in the plasma were measured with RT-PCR and Griess reagent respectively.The main results were as follows:1. Results of behaviors:Compared with the control group, UCMS induced significant depressive-like behaviors. These depressive-like behaviors were manifested with decreased sucrose preference, increased immobility time in forced swim test and reduced numbers of hole-searching times in spontaneous activity test. In contrast, there were no significant effects on some sickness related behaviors such as resting time, number of activity.1400w pretreatment abrogated these depressive-like behaviors.1400W pretreatment could abrogate these depressive-like behaviors. LPS model had obtained similar results.2. Results of molecular biology:(1) Compared with the control group, a significant upregulation of cortical iNOS mRNA expression was observed in UCMS-treated mice. This increase was completely blocked by1400w pretreatment.(2) Compared with the control group, the plasma nitrite level in UCMS-treated mice significantly increased. This increase was completely blocked by1400w pretreatment.3) Results of morphological experiment:Post-UCMS treatment, cortical neurons were shrunken with dark-staining and lost Nissl body. Pretreatment the mice with1400w protected cortical neurons from damage.We found the similar data in LPS models. |
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