ACTA NEUROPHARMACOLOGICA

Antioxidant effects of Orientin and Vitexin in Trollius Chinesis in D-galactose-induced mice model of aging

TIAN Qing-qing, WANG Shu-hua, AN Fang

2012, 2 (3): 1-6.

Abstract ( 2645 )

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Objective: To study the antioxidant effects of orientin and vitexin from Trollius chinensis Bunge. Methods: The aged mouse model was established through Daily intraperitoneal injection of D-galactose for 8 weeks was used to establish experimental aging in mice. Different groups of mice were treated with 40, 20 or 10 mg·kg^-1 orientin, vitexin, or a positive control (vitamin E) via intragastric administration for an additional 8 weeks. The total antioxidant capacity in the serum, activities of the antioxidant enzyme and the cell membrane transport ion ATP enzyme, and the level of malondialdehyde in the liver, brain and kidneys were determined. Results: Orientin, vitexin, and vitamin E produced a significant increase in total antioxidant capacity, in the serum, and the levels of superoxide dismutase, catalase and glutathione peroxidase, Na⁺-K⁺-ATP enzyme, and Ca²⁺-Mg²⁺-ATP enzyme in the liver, brain and kidneys. In addition, they significantly reduced the malondialdehyde levels in the liver, brain and kidney. The 40 mg·kg^-1dose of orientin and vitexin had similar antioxidant effects as vitamin E. Conclusion: Orientin and vitexin have anti-aging effects possibly through their antioxidant activities.

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Effects of Osthole on Neuronal Apoptosis and Cell Cycle in AD Rats

DONG Xiao-hua, MENG Xian-yong, ZHANG Li, YANG Jian-ming

2012, 2 (3): 7-14.

Abstract ( 3136 )

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Objective: To observe the influence of osthole on neuronal apoptosis and cell cycle in Alzheimer's disease (AD) rats and to study the neuroprotective effects and its mechanism. Methods: An intracerebroventricular (i.c.v.) injection of β-amyloid peptide (Aβ_25-35) was administrated to establish AD rat model. Osthole(12.5，25.0 mg·kg^-1) was injected intraperitoneally to rats and cognitive functions, neuronal apoptosis and cell cycle of AD rats were observed. Results: Osthole could improve spatial learning and memory abilities of AD rats, reduce neuronal apoptosis, increase the percentage of S phase cells, promote the G₂/M phase cells to divide further, strengthen the cell proliferation activity, regulate cell cycle and benefit to the maintenance of normal physiological function of neurons. Conclusion: Osthole hasneuronal protection through reducing neuronal apoptosis and regulating cell cycle, which may be one of mechanism of improving learning and memory disorder in AD rats.

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Transient Receptor Potential Melastatin 7 Involved in the Proliferation Induced by Platelet Derived Growth Factor and 5-HT in Pulmonary Artery Smooth Muscle Cells of Rates

GAO Hai-xia, QIAO Xiao-wen, DUN Jie-ning, DONG Ming-gang，XU Zhi-wei,ZHANG Hai-lin

2012, 2 (3): 15-21.

Abstract ( 2096 )

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Objective: To investigate the role of transient receptor potential melastatin7 (TRPM7) in platelet derived growth factor (PDGF) and 5-hydroxytryptamine (5-HT)-induced rat pulmonary artery smooth muscle cells (PASMCs) abnormal proliferation. Methods: PASMCAs were cultured with the explant technique. The expression of TRPM7 was evaluated by RT-PCR, western blot and whole-cell patch clamp. The proliferation of PASMCs was evaluated by MTT assay. TRPM7 inhibitor 2-APB was used to investigate the receptor mechanism of TRPM7-like current and the effects of TRPM7 in abnormal proliferation induced by PDGF and 5-HT. Results: RT-PCR and western blot showed that the TRPM7 mRNA and protein were detected in rat PASMCs. Electrophysiological results showed that the TRPM7 currents were detectable and that PDGF can increase the amplitude of TRPM7 inside and outside currents. 100 μmol•L^-1 2-APB inhibited PDGF and 5-HT-induced abnormal proliferation in rat PASMCs. Conclusion: TRPM7 participates in PDGF and 5-HT-induced abnormal proliferation in rat PASMCs and TRPM7 may be a new target for clinical treatment of pulmonary artery hypertension (PHA).

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Identification and Construction of Plasmid Expressing Exendin-4 mediated NT4 Leading Sequence

WANG Jun-hong, GUO Yong-hong, JIAO Yang, ZHANG Jing, XU Jing, XIE Xuan, YANG Guang-xiao, WANG Guan-ying, WANG Feng

2012, 2 (3): 22-28.

Abstract ( 2097 )

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Objective: To identify and construct a recombinant adeno-associated virus (AAV) vector that can secrete Exendin-4 mediated by NT4 leading sequence. Methods: ·L^-1). Conclusion: The recombinant virus pSSHG/NT4 - Exendin - 4 was successfully constructed by molecular cloning. The relatively high levels of recombinant virus were obtained. These results provide the basis for further studies that examine the function of Exendin-4.Exendin-4 cDNA was cloned by complementary primer/template PCR and T carrier cloning method. The Exendin-4 gene was linked to terminal of the signal peptide of NT4 leading sequence. The fusion gene of NT4- Exendin-4 was subcloned into the shuttle plasmid of pSSHG. The recombinant virus was transfected and packaged by human embryo kidney 293 cells and the virus titer was measured by quantitative dot-blot hybridization. Results: Exendin-4 cDNA cloning was confirmed by restriction enzyme digestion and DNA sequencing. The NT4 leading sequence and Exendin-4 cDNA clone were successful constructed in the same ORF and high titer of recombinant AAV was obtained (2.5×10⁹pfu

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Progress on the Neuroprotective Effects of Estrogen

SHEN Li-xia, ZHANG Li

2012, 2 (3): 29-36.

Abstract ( 3015 )

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In the past few years, there has been a growing interest in the neuroprotective effects of estrogen. An increasing amount of data suggest a neuroprotective role for estrogen; however, the molecular mechanisms whereby estrogen exerts these actions are unclear. In this review, we summarized the data supporting neuroprotection and the potential mechanisms that may contribute to these neuroprotective effects, including classical estrogen receptor activity, activation of the MAPK signaling transduction pathways, attenuation of glutamate receptor activation, antioxidant activity and regulation of mitochondrial function. Estrogen is a multi-faceted hormone modulating many aspects of neuronal function and no single mechanism of action has been elucidated for the neuroprotective effects of estrogens.

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Research Advances on Fate Decision of NSCs and Its Potential Target Modulation

MA Yin-zhong, CHEN Nai-hong

2012, 2 (3): 37-42.

Abstract ( 2825 )

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Neural stem cells (NSCs) are the source of neurons, oligodendrocytes and astrocytes in mammal neural system. In recent years, study base on the mechanisms of NSCs differentiation，proliferation and clinic research on neural degeneration diseases have been held great interests. Multiple cell regulation factors in the microenvironment co-regulate the self-renewal, differentiation and migration of NSCs. Among the factors, Notch，NF-κB and Wnt have been called “fate decision makers” and gained extensive attention. Each of them can control either differentiation or proliferation on their own. Here we reviewed the mechanisms of fate decision of three major signaling pathways: Notch, Wnt and NF-kB and summarized the potential drug targets and exogenous regulation factors, hoping to provide some guidance for future stem cell research.

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Chronic Dehydration and Regularly Drinking Water to Mitigate Age-Related Cognitive Impairment

LI Ting, QIANG Min, HE Rong-qiao

2012, 2 (3): 43-51.

Abstract ( 4509 )

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Age-related cognitive impairment undergoes a continuous progression: pre-mild cognitive impairment (preMCI), mild cognitive impairment (MCI) and Alzheimer’s disease (AD). So far, chronic dehydration is regarded as a common symptom for the patients with age-related cognitive impairment, in particular of those with AD. Monitored with an infrared-CCD camera, a marked decrease in the drinking frequency (P<0.05) and water consumption quantity (P<0.01) of 10-month old C57 BL/6 mice was observed in comparison with that of 1-month old counterparts. On the one hand, chronic dehydration for the patients may be resulted from their declined perception of “thirsty” and loss of memory. On the other hand, dehydration causes accumulation of cytotoxic metabolic compounds such as endogenous formaldehyde, worsening cognitive impairment. The interaction between dehydration and cognitive impairment leads to a vicious circle. Furthermore, chronic impairment of central nervous system due to the disorder of formaldehyde metabolism is believed as one risk factor for age-related impairment because of the increase in endogenous formaldehyde with aging (>65 years old) and in the hippocampus of Alzheimer’s patients. Regularly drinking water relieves not only chronic dehydration for aging people, but also significantly decreases the concentration of endogenous formaldehyde, which may offer protection of central nervous system. Therefore, building the habit to regularly drink water should be emphasized at the early stage to relieve chronic dehydration and scavenge cytotoxic metabolic products including formaldehyde for aging people, which might be beneficial to mitigate age-related cognitive impairment at its early stage.

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Oxidative Stress and Antioxidant Therapy after Acute Spinal Cord Injury

ZHANG Si, WANG Shuo-yu, LI Hua-nan, ZHANG Guo-fu, GU Bing

2012, 2 (3): 52-64.

Abstract ( 3589 )

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Acute spinal cord injury can lead to severe motor and sensory dysfunction. Oxidative stress caused by free radical plays an important role in the pathophysiology of secondary injury. Inhibition of biological macromolecules peroxidation damage through antioxidant intervention may be an effective strategy for drug therapy of spinal cord injury. This paper mainly introduces the cause, process and participation of oxidative stress in the pathophysiological mechanism of acute spinal cord injury, and also reviews the recent advances in antioxidant drug research, aiming to facilitate the discovery of safe and effective antioxidant drugs for potential treatment of acute spinal cord injury.

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