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Methods and Evaluation of Animal Models of Cerebral Ischemia and Cerebral Ischemia Reperfusion Injury Wang Shu, Zhang Li Acta Neuropharmacologica    2011, 1 (3): 31-40.   Abstract （5192）      PDF（pc） （1126KB）（5941）       Knowledge map    Save Cerebrovascular disease is a clinically common disease and frequently-occurring disease. The selection and application of reliable animal models are particularly important in studies for the prevention and treatment of cerebrovascular disease. The types, operation procedures of models, and characteristics of the global cerebral and focal cerebral ischemia and cerebral ischemia reperfusion injury in different animal models were discussed in detail in this paper. The improved Himori method (the model of cerebral ischemia reperfusion was produced in mice by temporarily obstructing bilateral common carotid arteries) and some key steps were especially presented in detail. The evaluation of the application characteristics of existing animal models will help to select the appropriate models of cerebral ischemia and cerebral ischemia reperfusion for studying cerebrovascular disease. Reference | Related Articles | Metrics | Comments（0）

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In Vivo Application of Two-photon Microscopy in Neuropharmacological Research ZHAO Jun,WANG Jin-hui Acta Neuropharmacologica    2012, 2 (1): 45-64.   Abstract （5126）      PDF（pc） （6504KB）（5903）       Knowledge map    Save Two-photon microscope is an useful and advanced tool for noninvasive deep fluorescence imaging in the intact brain tissue of living animals. Due to nonlinear two-photon effects, two-photon microscope enables long-term imaging in vivo with deeper detection, higher signal-to-noise ratio and lower photodamage, compared to wide-field and confocal microscopy. Two-photon microscopy can provide high-resolution images to study cellular and subcellular structure and function, including morphology, mobility and intracellular ions of cells. On the other hand, large scale two-photon imaging of cell population reveals the network construction and activity dynamics with single-cell resolution, which makes two-photon microscopy a high throughput tool in system pharmacology. Moreover, two-photon microscopy can offer some precise optical operations, such as photolysis, photoactivation, phototransfection and photodamage. Here, we give an introduction to the principles of two-photon microscopy and its in vivo applications in neuroscience and neuropharmacology researches. Reference | Related Articles | Metrics | Comments（0）

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Distinct Roles and Modulations of Synaptic and Extrasynaptic NMDA Receptors CHU Shi-feng, CHEN Nai-hong Acta Neuropharmacologica    2011, 1 (5): 40-48.   Abstract （8457）      PDF（pc） （790KB）（4530）       Knowledge map    Save N-Methyl-D-Aspartate receptor（NMDA receptor） has been considered as a double-edged sword in central nervous system. On the one hand, it mediates the calcium influx, promotes the synaptic plasticity and improves the neural excitatory. On the other hand, excessive opening of NMDA receptor causes calcium overload in neurons, disturbing the homeostasis and inducing the apoptosis. However, growing number of studies demonstrated that the distinct roles of NMDA receptor do not totally depend on its opening degree, but also on its locations where different signaling pathways are triggered. Synaptic NMDA receptors activate the nuclear calcium signaling pathways to protect the neurons; whereas activation of extrasyanptic NMDA receptor starts the apoptosis or death pathway. The imbalance between the two pathways accounts partially for pathogenesis in neural diseases, such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease. In conclusion, the currently available evidence has provided a new clue for the treatment of neurodegenerative disease. Reference | Related Articles | Metrics | Comments（0）

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Research Progress on Pharmacologic Actions of Curcumin in Central Nervous System LI Gao-wen, XU Ying, KU Bao-shan, PAN Jian-chun ACTA NEUROPHARMACOLOGICA    2011, 1 (2): 48-57.   Abstract （6710）      PDF（pc） （1221KB）（4530）       Knowledge map    Save Curcumin, an active yellow polyphenol pigment of turmeric, belongs to polyphone compound. Quantities of research have proved its pharmacologic actions in peripheral systems, such as antiatherosclerosis, antineoplasms, antidiabetes; In recent years, people have also found curcumin’s therapeutic effects on some neurodegenerative diseases and affective disorders, such as alzheimer’s, parkinson’s, depression, epilepsy and anxiety. As a powerful antioxidative agent, curcumin can modulate the balance of redox and reduce the formation of responsive oxidative species（ROS）, which results in the neuroprotective effect. In addition to these, the neuroprotective effect of curcumin is involved in regulating signal molecules, such as NF-κB Nrf2 p-MEK,p-ERK,c-fos,APP,BACE1.Curcumin can also affect the BDNF/TrkB-MAPK/PI-3K-CREB pathway to regulate the neuroplasticity, cell vitality and antiapoptosis. This review summarizes the effects and possible mechanism of curcumin on neurodegenerative diseases, cerebral ischemia, traumatic brain injury and affective disorders such as depression and anxiety. Reference | Related Articles | Metrics | Comments（0）

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Behavioral Pharmacology: History and Current Status LI Jun-xu Acta Neuropharmacologica    2011, 1 (1): 55-64.   Abstract （6208）      PDF（pc） （1258KB）（4159）       Knowledge map    Save   As a branch of pharmacology，behavioral pharmacology has been stepping into its 50s. Since the publication of the hallmark paper of this field in 1955，behavioral pharmacology has seen a steady，vibrant and healthy development. This review traced back into 1950s，summarizing the major events during the history of behavioral pharmacology，and discuss the current status in this field. The paper also discussed several issues related to behavioral pharmacology research. Reference | Related Articles | Metrics | Comments（0）

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Mitochondria and Neurodegenerative Diseases Zhou Xiao-wen, Su Chao-fen, Luo Huan-min ACTA NEUROPHARMACOLOGICA    2011, 1 (3): 41-46.   Abstract （4984）      PDF（pc） （1083KB）（4111）       Knowledge map    Save The neurodegenerative diseases are usually caused by the loss of the neurons and/or their myelin sheath, but the pathogenesis of these diseases are still indeterminate. Studies so far has proved that mitochondrial dysfunction and energy metabolism disorders are early pathological phenomena. This review concentrates on two of the most prevalent neurodegenerative diseases: Alzheimer’s disease (AD) and Parkinson’s disease (PD) and would be aimed to discuss the role of mitochondrial in pathogenesis of neurodegenerative diseases, providing new direction for further research. Reference | Related Articles | Metrics | Comments（0）

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Methods and Evaluation of Animal Models of Induced Cough ZHANG Dan-shen Acta Neuropharmacologica    2011, 1 (2): 35-41.   Abstract （4516）      PDF（pc） （1062KB）（4087）       Knowledge map    Save The cough induced by many factors is a common symptom of a variety of respiratory diseases. Ideal animal models are needed not only for the studies on the incidence and control mechanisms of the cough reflex, and etiology and pathogenesis of the cough, but also for the research and development of effective antitussives and the treatment of human cough. In this review, the animal models of induced cough were described in detail and evaluated to provide some guidance for related basic and clinical research and applications. Reference | Related Articles | Metrics | Comments（0）

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Establishment about several anti-oxidant models of microplate quantification suitable for drug-screening and their stability testing ZHANG Dan-shen Acta Neuropharmacologica    2011, 1 (1): 45-51.   Abstract （4745）      PDF（pc） （1451KB）（4008）       Knowledge map    Save Objective: To establish a series of anti-oxidant models of microplate quantification suitable for the drug screening. Methods: By using SpectraMax M5 continuous spectrum enzyme sign reflectoscope reflector，the anti-oxidant microplate quantification experiment modles of anti-DPPH oxidation activity，elimination hydroxy free radical，reduction ability determination，and lipid peroxidation were established. Results: All of the anti-oxidant microplate quantification experiment modles had more common characteristices of the good stability，the fewer reagent types and quantity，simple operation and step，the good repeatability，and so on. Relatively speaking，the two anti-oxidant modles of anti-DPPH oxidation activity，reduction ability determination had more advantage in these experiment modles，and had more suitable for initially screening experiment of the anti-oxidant drug as basic research. Conclusion: These four modles of the anti-oxidant microplate quantification may be widely applied in anti-drug screening，especially high-throughput screening research. Reference | Related Articles | Metrics | Comments（0）

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Review on Synaptic Plasticity Related Proteins GUO Min, LI Gang ACTA NEUROPHARMACOLOGICA    2013, 3 (6): 57-64.   Abstract （3924）      PDF（pc） （1304KB）（3948）       Knowledge map    Save Synaptic plasticity is not only the molecular basis of learning and memory，but also the molecular mechanisms of signal transduction in the nervous system diseases. The synapses is a sensitive parts in synaptic plasticity，presynaptic and postsynaptic membrane accumulate many signal molecules that can lead to synaptic plasticity regulation. These molecules are very necessary for nerve transmission in synaptic parts. Recently, the research on the mechanisms of synaptic plasticity is mainly focus on the function of the presynaptic and postsynaptic related proteins and the nerve cytoskeletal proteins in signal pathway. Here is to review the latest progress in the synaptic plasticity related proteins. Reference | Related Articles | Metrics | Comments（0）

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Involvement of Kir6.2-composing ATP-sensitive potassium channels in phencyclidine-induced negative symptoms of schizophrenia DAI Ting, CHEN Zhong-Guo, DUAN Lei, DING Jian-Hua, FAN Yi, HU Gang ACTA NEUROPHARMACOLOGICA    2011, 1 (1): 31-38.   Abstract （5030）      PDF（pc） （1811KB）（3855）       Knowledge map    Save Objective: ATP-sensitive potassium (K-ATP) channels are crucial for dopaminergic and glutamatergic transmission，which has been demonstrated to be the important feature of pathophysiology in schizophrenia. We studied the effects of K-ATP channels on the phencyclidine (PCP)-induced changes in the forced swimming test (FST，an animal model of negative symptoms of schizophrenia)，using mice with knockout of the Kir6.2 (a pore-forming subunit of neuronal K-ATP channel). Methods:After repeated PCP (10 mg·kg-1，i.p. daily for 14 days) administration，The FST were used to assess depression-related behaviors associated with negative symptoms. Striatal dopamine and dopamine turnover were measured by high pressure liquid chromatography with electrochemical detection. Cell proliferation in the subgranular zone (SGZ) was determined by bromodeoxyuridine immunohistochemistry. The expressions of total Akt and phosphorylation Akt were evaluated using Western blot. Results: After repeated PCP administration，the enhancement of immobility induced by the FST was attenuated in Kir6.2 knockout mice.  Meanwhile，Kir6.2 knockout decreased striatal dopamine turnover，whereas wild-type mice exhibited an augmentation in response to PCP treatment. Furthermore，Kir6.2 knockout could prevent the inhibition of neural stem cell proliferation in the SGZ and suppressed the PCP-induced phosphorylation of AktSer473. Conclusion: These results suggest a possible implication of Kir6.2-composing K-ATP channels dysfunction in the pathogenesis of negative symptoms associated with schizophrenia. Reference | Related Articles | Metrics | Comments（0）

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Roles of Adenomatous Polyosis Coli in the Early Developing Cerebral Cortex ZUO Wei, JI Hui, WANG Wen ACTA NEUROPHARMACOLOGICA    2011, 1 (2): 42-47.   Abstract （4730）      PDF（pc） （1009KB）（3573）       Knowledge map    Save Adenomatous polyosis coli（APC）is a large multifunctional protein known to be important for Wntβ-catenin signalling, cytoskeletal dynamics, and cell polarity. In the developing cerebral cortex, APC is expressed in proliferating cells and its expression increases as cells migrate to the cortical plate. In this article, we summarized the roles of APC in the early developing cerebral cortex. APC is required for multiple aspects of early cerebral cortical development, including the regulation of cell number, interkinetic nuclear migration, cell polarity, and cell type specification. Reference | Related Articles | Metrics | Comments（0）

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Progress in Understanding the Pathogenesis of Alzheimer’s Disease XUE Xiao-yan, GUO Xiao-hua, LI-Min, LUO Huan-min ACTA NEUROPHARMACOLOGICA    2011, 1 (6): 37-47.   Abstract （3459）      PDF（pc） （1307KB）（3550）       Knowledge map    Save Although thepathogenesis of Alzheimer’s Disease (AD) is unclear, several hypotheses have been proposed, including the β-amyloid cascade theory, tau protein hypothesis, inflammation hypothesis and oxidative stress theory. This review summarized the widely-accepted new viewpoints on the pathogenesis of AD． Reference | Related Articles | Metrics | Comments（0）

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Cultivation and identification of neural stem cells cultivated by the methods of neurospheres and adherent monolayer cells HAO Jun-Rong, ZHANG Li, QIN Zheng-Hong Journal of Materials Sciences & Technology    2011, 1 (1): 51-55.   Abstract （5718）      PDF（pc） （9034KB）（3549）       Knowledge map    Save Objective:AIM To explore two methods of culturing mouse embryo neural stem cells in vitro and identification of their differentiation． Methods: The neural stem cells were derived from the cortex tissue of mouse embryo at gestation day of 14～16 with two methods: culturing of neurosphere in floating and culturing of monolayer adherent cells. To observe the development of the neural stem cell，the expression of the stem cell marker Nestin and the neural marker MAP-2 and the glial marker GFAP was examined with immunofluorescence.  Results: The cultured neural stem cells proliferated．The maintenance of stem cell property was preserved with both methods as revealed by Nestin immunofluorescence. These stem cells are able to differentiate into glial (GFAP positive) and neuronal lineage (MAP-2positive). Conclusion: With the help of growth factors and serum-free technique，the mouse neural stem cells cultivated by methods of neural stem cell spheres and adherent monolayer cells，have potential of proliferation and differentiation. Reference | Related Articles | Metrics | Comments（0）

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Animal Models of Alzheimer’s Disease and Pharmacotherapeutics JIN Miao, AN Hong-mei Acta Neuropharmacologica    2011, 1 (6): 28-36.   Abstract （5534）      PDF（pc） （1296KB）（3481）       Knowledge map    Save This paper reviewed recent progress in animal models of Alzheimer's disease (AD) and pharmacotherapy of AD. Herein, we summarized the different types of AD animal models based on the pathogenesis of AD, and concluded that there is a lack of full demonstration of the etiology and pathological changes of AD disease in animal models. We also summarized the current available medication treatments of AD. Aβ and Tau protein are still the research focus in the field of AD treatment. Chinese medicine also plays a certain role in the treatment of AD, and shows a good prospect. Reference | Related Articles | Metrics | Comments（0）

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Progress in Understanding the Relevance of Learning and Memory to Estrogen and Glu-NMDA Receptor Pathway ZHANG Xia-wei, ZHANG Dan-shen ACTA NEUROPHARMACOLOGICA    2011, 1 (6): 48-59.   Abstract （3982）      PDF（pc） （1338KB）（3464）       Knowledge map    Save Besides maintaining the female secondary sexual characteristics, estrogen also plays important roles in the nervous system, especially in the brain: it can protect tissue from cerebral ischemia reperfusion injury and reduce infarct area by suppressing free radical formation, and can also regulate the release of excitatory amino acids. As an antioxidant, estrogen can protect the nervous system by regulating the body’s redox homeostasis. In addition, estrogen can play its neuroprotective role through estrogen receptors (ER). ER-α and ER-β, two typical ER subtypes that are mainly located in the nucleus, are both expressed in the cerebral cortex and hippocampus. It has been found that ER-α level in the cortex and hippocampus of ovariotomy rats is decreased accompanying decreased learning and memory. LTP, synaptic density and learning and memory are all affected in ER-β gene knock-out mice. NMDA receptor is critical in learning and memory and is coexpressed in hippocampus with estrogen receptors. Estrogen may activate ERK1/2 signal transduction pathway through membrane estrogen receptors, thus inducing the phosphorylation of the NR2B subunit of NMDA receptor to activate NMDA receptor. In addition, the synaptic plasticity can be affected by estrogen and its receptors, as well as by NMDA receptor. Reference | Related Articles | Metrics | Comments（0）

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Neuroprotective role of the Alpha 2-Adrenergic Agonist Dexmedetomidine in Ischemic Cerebrovascular Disease HU Min, HE Zhi ACTA NEUROPHARMACOLOGICA    2011, 1 (5): 49-55.   Abstract （5155）      PDF（pc） （714KB）（3449）       Knowledge map    Save Ischemic cerebrovascular disease is a common and frequently encountered disease with high disability and mortality rates, and has severe effects on human’s health and quality of life. Cerebral hypoxic ischemia leads to an increase in the number of damaged or dead neurons. Recent studies have provided considerable evidence that alpha 2-adrenergic agonists can protect the brain neuron from cerebral ischemia/reperfusion injury. However, the exact mechanisms of this protection remain unknown. Activation of the alpha 2-adrenergic receptor may be involved. Dexmedetomidine is a highly selective agonist of the alpha 2-adrenergic receptors with neuroprotective effects. This article reviews the pathophysiological process of ischemic cerebrovascular disease, the molecular pharmacology and the neuroprotective mechanisms of dexmedetomidine. Reference | Related Articles | Metrics | Comments（0）

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Effects of nicotine analog ZY-1 on β-amyloid production and learning and memory in transgenic Alzheimer disease mice NIE Hui-Zhen, WANG Ze-Jian, ZHAO Wen-Juan, LU Jin-Miao, ZHANG Can, LUO Qing-He, WANG Yu-Liang, GAO Xiang, YIN Ming Acta Neuropharmacologica    2011, 1 (1): 26-31.   Abstract （5753）      PDF（pc） （1522KB）（3406）       Knowledge map    Save Objective: To observe the effects of ZY-1, a nicotine analogue, on in vitro receptor binding and β-amyloid (Aβ) production and in vivo transgenic Alzheimer’s disease mice. Methods: Receptor binding assay was carried out in SH-EP1-α4β2 nAChR cell line highly expressing α4β2 nAChR; Western blotting was used to detect the effects of ZY-1 on amyloid protein production in the SH-EP1-α4β2 nAChR cell line transfected with APP695 plasmid; and effects of ZY-1 on learning and memory were measured in B6C3-Tg（APPswe, PSEN1dE9）85Dbo/J mice. Results: 1. Receptor binding assay showed that Ki is 21.5 n mol•L-1, suggesting specific binding of ZY-1 to α4β2 nAChR; 2. ZY-1(1 μmol•L-1) reduced intracellular production of Aβ; 3. Middle (0.50 mg•kg-1) and high dose (0.75 mg•kg-1) of ZY-1 improved learning and memory of transgenic mice in Morris water maze and platform test. Conclusion: ZY-1 might be of potential to be an AD therapeutic agent, but the druggability remains to be further confirmed. Reference | Related Articles | Metrics | Comments（0）

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Glucocorticoids and Hippocampal Structural Plasticity CHEN Lin，DU Li-jun，ZHAO Yu-nan Acta Neuropharmacologica    2011, 1 (2): 58-64.   Abstract （4954）      PDF（pc） （1023KB）（3378）       Knowledge map    Save Chronic high dose glucocorticoid exposure produces the major disruption to the hippocampal structural plasticity（such as plastic changes in spine and dendrite morphology, astrocyte as well as adult neurogenesis）, which can be reversed by anti-glucocorticoid therapy,indicating that glucocorticoids play a crucial role in chronic stress-induced impairment of hippocampal structural plasticity. Thus, one way to avoid the variable effects of stress exposure on animal behavior is developed by using exogenous corticosterone administration as a means to enhance efficiency and stability of animal model. Interestingly, short-term or acute glucocorticoid exposure has the ability to enhance structural plasticity, suggesting that the regulation of glucocorticoids on hippocampal structural plasticity is bidirectional. Reference | Related Articles | Metrics | Comments（0）

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Research Advances in Using Ginseng to Prevent and Treat Parkinson’s Disease LI Dong-wei, DOU De-qiang ACTA NEUROPHARMACOLOGICA    2011, 1 (4): 55-64.   Abstract （4856）      PDF（pc） （1686KB）（3345）       Knowledge map    Save The current research in Parkinson’s disease and progress in using of ginseng to treat Parkinson’s disease，and mechanisms of ginsenosides-induced protection of dopaminergic neurons in substantia nigra were reviewed，which lay a foundation for the reasonable application of ginseng in the treatment of Parkinson’s disease. Ginsenosides can play an important role in protecting dopaminergic neurons by countering oxidative stress，inhibiting Ca2+ channel and blocking the signaling pathways of neurons apoptosis. Reference | Related Articles | Metrics | Comments（0）

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Progress in Studies of Glutamatergic Neurotransmission in the Pathogenesis of Depression LI Jing, SUN Jian-dong, YUAN Yu-he, CHEN Nai-hong Acta Neuropharmacologica    2014, 4 (1): 20-24.   Abstract （3594）      PDF（pc） （893KB）（3293）       Knowledge map    Save The “monoamine hypothesis” of depression, which posits that depression is caused by decreased monoamine function in the brain, originated several decades ago. Although these monoamine-based agents are potent antidepressants, the cause of depression is far from being a simple deficiency of central monoamines. The glutamatergic system also plays important roles in the pathophysiology of major depressive disorder. This paper summarizes the physiological characteristics of glutamate in the brain, glutamatergic abnormalities in depression andantidepressants acting on the glutamatergic system. Reference | Related Articles | Metrics | Comments（0）