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26 February 2018, Volume 8 Issue 1 Previous Issue    Next Issue

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New Strategies for the Drug Development of Anti-cerebral Ischemia —Advances in the Etiology and Drug Development of Acute Cerebral Ischemia DU Guan-hua，ZHANG Wen，DU Li-da，MA Yin-zhong，LI Li，WANG Yue-hua 2018, 8 (1):  1-8.  DOI: 10.3969/j.issn.2095-1396.2018.01.001 Abstract ( 207 )   PDF (1217KB) ( 395 )   Acute cerebral ischemia （stroke） is a major disease which threat to people’s health because of its high incidence，high mortality and high morbidity. Of particular concern is that the clinical application of a serious lack of prevention and treatment of drugs，and a large number of research and development of drugs has not been successful. This paper analyzes the current status of prevention and treatment of acute cerebral ischemia drugs and the reasons for its lack of success. It is proposed that a new strategy is necessary for new drug development and research. Based on the recognization of the analysis of the disease pathology and drug research，we suggested the disease pathogenesis and features based strategy and pathological process based drug development strategies. References | Related Articles | Metrics

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Pharmacological Progress of Ganoderma on Anti-aging and Anti-Alzheimer’s Disease LIN Zhi-bin 2018, 8 (1):  9-15.  DOI: 10.3969/j.issn.2095-1396.2018.01.002 Abstract ( 597 )   PDF (1372KB) ( 552 )   Present article reviewed the pharmacological progress on anti-aging and anti- Alzheimer’s disease of Ganoderma（Lingzhi）. G.lucidum polysaccharide significantly enhanced the immunity in aged mice，which involved that increasing plaque forming cells，promoting T and B lymphocyte proliferation reaction and mixed lymphocyte reaction，and enhancing interleukin-2 production in aged mice. The immune-enhancing effect of G.lucidum polysaccharides may relate to increase DNA polymeraseαactivity of spleen cells in aged mice. G.lucidum polysaccharide can delay the aging of cells，organs and tissues by anti-oxidative stress. G. lucidum polysaccharides，triterpenes and spores can improve of learning and memory function and histopathological injury of the hippocampus in animal model of Alzheimer disease，and its mechanism is closely related to antioxidative and scavenging free radicals effect by Ganoderma（Lingzhi） References | Related Articles | Metrics

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Hepcidin and Iron-associated Neurodegenerative Disorders MA Juan，ZHANG Fa-li，QIAN Zhong-ming 2018, 8 (1):  16-22.  DOI: 10.3969/j.issn.2095-1396.2018.01.003 Abstract ( 320 )   PDF (1359KB) ( 250 )   The abnormally increased iron in the brain is an initial cause of neuronal death at least in some neurodegenerative. By binding to a unique cellular iron exporter，ferroportin 1 result in its endocytosis and degradation，and inhibit the release of duodenal iron to plasma and inhibit the release of iron from macrophage，then regulat the iron homeostasis of the body. Therefore，hepcidin is a new target for pharmacological intervention in these diseases. Reducing iron to normal level or hampering iron to increase with age in the brain is a promising therapeutic strategy for all iron-associated neurodegenerative disorders. Recent studies demonstrated that increasing hepcidin level in the brain could significantly reduce brain iron contents by regulating the expression of iron transport proteins located in the brain-blood barrier （BBB），neurons and astrocytes. This review mainly discusses the role of hepcidin in the brain and its potential therapeutic role in the disease，providing a new strategy for the prevention and treatment of those diseases. References | Related Articles | Metrics

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Recent Advance on Sleep-Wake Regulation Based on Novel Techniques for Specific Manipulations of Neuron Activities YANG Yan-fei，HUANG Zhi-li 2018, 8 (1):  23-34.  DOI: 10.3969/j.issn.2095-1396.2018.01.004 Abstract ( 278 )   PDF (6249KB) ( 487 )   One-third of life is spent in sleep，but why we need to sleep and how sleep-wake cycles regulate are still mysterious. The previous used pharmacology， immunohistochemistry，neuronal damage and other traditional research methods have partly revealed several brain areas related to sleep-wake . As it familiar to us that hypothalamic ventrolateral preoptic area and parafacial zone are sleep-promoting areas，while the midbrain dorsal raphe，locus coeruleus，tuberomammillary nucleus，lateral hypothalamus and basal forebrain wake-promoting areas. Though these brain regions that regulate sleep-wake are interacting，they also closely linked to maintain normal sleep-wake cycles. However，due to the poor spatial specificity and selectivity by traditional technology，it is tough to accurately explore more new sleep-wake related brain areas and neurons. In recent years，with the application of specific manipulation of neuron activity，researchers can specifically control different kinds of neuronal activities in the brain，including GABAergic，glutamatergic，and cholinergic neurons to study their roles in sleep-wake regulations，or to identify new brain regions. This review focuses on the new progress in the study of sleep-wake regulation mechanism based on optogenetic and chemogenetic techniques. References | Related Articles | Metrics

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An Update on Allosteric Modulator of Sigma-1 Receptors: Potential Applications WANG Yun，ZHEN Xue-chu 2018, 8 (1):  35-44.  DOI: 10.3969/j.issn.2095-1396.2018.01.005 Abstract ( 306 )   PDF (2936KB) ( 427 )   Sigma-1 receptors are involved in the pathophysiological process of several neuropsychiatric diseases. Allosteric modulation of receptor represents an important mechanism for receptor functional regulation. Compared to orthodox ligands of sigma-1 receptor，allosteric modulator has tremendous advantages in selectivity and safety. Thus，development of allosteric modulation toward sigma-1 receptors has become a new approach for treatment of neuropsychiatric diseases. Here，we summarized the progress of biological functions and developed ligands of sigma-1 receptors，and discussed the potential applications of novel allosteric modulator in some neuropsychiatric diseases. References | Related Articles | Metrics

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Establishment and Behavior Evaluation of Rat Chronic Unpredictable Mild Stress and Mouse Social Defeat Models XIAO Ting, MA Tian-yang, XU Xiang-qing, WANG Ke-wei 2018, 8 (1):  45-53.  DOI: 10.3969/j.issn.2095-1396.2018.01.006 Abstract ( 320 )   PDF (1677KB) ( 373 )   Objective： To study the pathogenesis of major depressive disorder （MDD），it is necessary to establish animal models of depression. There are two common chronic depressive models that are chronic unpredictable mild stress （CUMS） and social defeat （SD）. In this study，we modified these models and compared the advantages and disadvantages of the two models to establish a more stable model of depression. Methods： For CUMS model，rats were treated with randomized two stressors last for 28 days. Stressors include overnight illumination，tail pinch，wet cage，crowding cage，ice water swimming，water and food deprivation. Rats were divided into three groups of blank Control，CUMS and CUMS + Fluoxetine （10 mg·kg-1） as positive control. For SD model，social defeat stress factors include 5 to 10 min physical attack and 24 hours sensory interaction. Mice were divided into Control and SD groups. After modeling， we adopt sucrose preference，immobility time of Forced Swimming Test and social interaction ratio to study whether the model is successful. Results： There was a significant decrease of sucrose preference （69.3%±3.6%，n=27） and significant increase of immobility time of Forced Swimming Test （131.2±5.8 s，n=27） in CUMS rats，as compared with control group of rats with sucrose preference （81.0%±3.2%，n=17，P<0.05） and immobility time （105.1±8.2 s，n=17， P<0.05）. The sucrose preference （82.1%±3.9%，n=10） and immobility time of Forced Swimming Test （108.3±9.7 s，n=10） were no significant change in CUMS + Flu group rats，as compared with control group. Mice in social defeat showed that social interaction ratio below 1 （determined by SIR<1，SIR=Duration in interaction zone of target absent phase/ Duration in interaction zone of target present phase），as compared with social interaction ratio greater than 1 in control group. Moreover，SIR of SD mice was significantly lower （69.2%±2.4%，n=16） than that of control group （78.6%±3.2%，n=9，P<0.05）. Conclusions： Based on the core criteria of sucrose preference，models of CUMS in rats and SD in mice are successfully established，whereas the social defeat model is more reproducible and consistent. References | Related Articles | Metrics

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Research Progress of the Role and Underlying Mechanism of Dynorphin/κ Opioid Receptor in the Development of Depression ZAN Gui-ying，SUN Xiang，LI Qing-lin，LIU Jing-gen 2018, 8 (1):  54-64.  DOI: 10.3969/j.issn.2095-1396.2018.01.007 Abstract ( 703 )   PDF (1421KB) ( 486 )   Depression is a serious mental disorder charactered by high prevalence，major depression always result in great harm to society. At present，the most popular antidepressants including monoamine reuptake inhibitors have some deficits including slower effect，side-effect. At the same time，some patients do not response adequately to the antidepressant medication. The development of drugs targeting opioid receptor has shown promising prospect，clinical studies  have demonstrated that κ opioid receptor antagonist Buprenorphine could possibly cure depressive symptoms in patients with classical antidepressants treatment-resistant depression. In present review，we discuss the recent progress of the role of κ opioid receptor in different brain regions during the development of depression，and introduce the association between dynorphin/κ opioid receptor and CRF as well as monoamine system. Furthermore，we briefly introduce the upstream and downstream molecules of κ opioid receptor that contribute to the development of depression. References | Related Articles | Metrics