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国家自然科学基金(81221002)

作品数:11 被引量:32H指数:4
相关作者:崔彩莲吴鎏桢卞希玲高凯王克威更多>>
相关机构:北京大学北京大学第一医院更多>>
发文基金:国家自然科学基金国家重点基础研究发展计划全球变化研究国家重大科学研究计划更多>>
相关领域:医药卫生环境科学与工程生物学更多>>

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11 条 记 录,以下是 1-10
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Canonical Wnt signaling pathway is involved in astrogliosis via activation of Lrp6
Mechanical injury of the brain has been studied for decades utilizing in vitro model of astrocytes,regarding t...
Siqi LIChunzhang YANGZhengping ZHUANGAlbert Cheung Hoi YU
关键词:ASTROCYTEBETA-CATENINWNT
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Targeting voltage-gated Kv7/KCNQ/M-channel for therapeutic potential of neuropsychiatric disorders
2014年
M-type potassium current (IM) was initially isolated from sympathetic neurons in 1980 and named as it was inhibited by muscarine. In 1998, the molecular identity of M-current was revealed to be heterotetramers of KCNQ2 and KCNQ3 subunits, whose mutations cause neonatal epilepsy. Reduction of voltage-gated KCNQ2/3 K+ channel (M-channel) activity leads to neuronal byperexcitability that defines the fundamental mechanism of neurological disorders such as epilepsy and pain. Thus, suppression of neuronal hyperexcitability by activation of KCNQ2/3 channels serves the basis for development of the channel openers for treatment of epilepsy and pain. The well-known KCNQ opener is retigabine (Potiga) that was approved by FDA as an antiepileptic drug in 2011. Recent studies also provide evidence that KCNQ2/3 channel openers are effective in animal models of bipolar disorder, anxiety and schizophrenia, whereas KCNQ2/3 inhibitors, on the other hand, are indicated for improvement of learning and memory in animal models. We recently designed and validated a novel series of pyrazolo [1,5-a]pyrimidin-7(4H)-ones (PPOs) that selectively activate KCNQ2/3 and show antiepileptic and analgesic activity in vivo. Up to date, all the progress made enforces the view that targeting voltage-gated KCNQ/M-channel may provide therapeutic potential for treatment of neuropsychiatric disorders.
卞希玲王克威
关键词:RETIGABINEEPILEPSYPAIN
Elevated Neurosteroids in the Lateral Thalamus Relieve Neuropathic Pain in Rats with Spared Nerve Injury被引量:6
2016年
Neurosteroids are synthesized in the nervous system from cholesterol or steroidal precursors imported from peripheral sources. These compounds are important allosteric modulators of γ-aminobutyric acid A receptors (GABAARs), which play a vital role in pain modulation in the lateral thalamus, a main gate where somatosensory information enters the cerebral cortex. Using high-perfor mance liquid chromatography/tandem mass spectrometry, we found increased levels of neurosteroids (pregnenolone, progesterone, deoxycorticosterone, allopregnanolone, and tetrahydrodeoxycorticosterone) in the chronic stage of neuropathic pain (28 days after spared nerve injury) in rats.The expression of the translocator protein TSPO, the upstream steroidogenesis rate-limiting enzyme, increased at the same time. In vivo stereotaxic microinjection of neurosteroids or the TSPO activator AC-5216 into the lateral thalamus (AP -3.0 mm, ML 4-3.0 mm, DV 6.0 mm) alleviated the mechanical allodynia in neuropathic pain, while the TSPO inhibitor PK 11195 exacerbated it. The analgesic effects of AC-5216 and neurosteroids were sig- nificantly attenuated by the GABAAR antagonist bicuculline. These results suggested that elevated neurosteroids in the lateral thalamus play a protective role in the chronic stage of neuropathic pain.
Meng ZhangJia LiuMeng-Meng ZhouHonghai WuYanning HouYun-Feng LiYuxin YinLemin ZhengFeng-Yu LiuMing YiYou Wan
关键词:NEUROSTEROIDSTHALAMUS
Crystal structure of the N-terminal ankyrin repeat domain of TRPV3 reveals unique conformation of fi nger 3 loop critical for channel function被引量:3
2013年
In all six members of TRPV channel subfamily,there is an ankyrin repeat domain(ARD)in their intracellular N-termini.Ankyrin(ANK)repeat,a common motif with typi-cally 33 residues in each repeat,is primarily involved in protein-protein interactions.Despite the sequence similarity among the ARDs of TRPV channels,the struc-ture of TRPV3-ARD,however,remains unknown.Here,we report the crystal structure of TRPV3-ARD solved at 1.95Åresolution,which reveals six-ankyrin repeats.While overall structure of TRPV3-ARD is similar to ARDs from other members of TRPV subfamily;it,however,features a noticeable fi nger 3 loop that bends over and is stabilized by a network of hydrogen bonds and hydrophobic pack-ing,instead of being fl exible as seen in known TRPV-ARD structures.Electrophysiological recordings demonstrated that mutating key residues R225,R226,Q255,and F249 of fi nger 3 loop altered the channel activities and pharmacol-ogy.Taken all together,our findings show that TRPV3-ARD with characteristic fi nger 3 loop likely plays an im-portant role in channel function and pharmacology.
Di-Jing ShiSheng YeXu CaoRongguang ZhangKeWei Wang
关键词:KERATINOCYTE
AQP5 is differentially regulated in astrocytes during metabolic and traumatic injuries
Water movement plays vital roles in both physiological and pathological conditions in the brain.Astrocytes are...
Rui Chao CHAIJiao Hua JIANGAnn Yuen Kwan WONGFeng JIANGKai GAOGreg VATCHERAlbert Cheung Hoi YU
关键词:AQUAPORINMCAO
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Acupuncture Mechanisms: Anesthesia, Analgesia and Protection on Organ Functions被引量:3
2015年
Acupuncture, as a healing art in traditional Chinese medicine, has been widely used to treat various diseases. In the history of acupuncture anesthesia, in the past decades, mechanisms of acupuncture analgesia has been widely investigated, and in recent years, acupuncture protection on organ functions has attracted great interest. This review summarized the research progress on mechanisms of acupuncture for analgesia and its protection against organ function injury in anesthesia, and its perspective of analgesia, immunomodulation, neuroendocrine regulation and multiple organ protection. The current evidence supports that acupuncture analgesia and its organ protection in anesthesia is associated with the integration of neuroendocrine-immune networks in the level of neurotransmitters, cytokines, hormones, neuronal ensembles,lymphocytes, and endocrine cells. Although the mechanisms of acupuncture analgesia and its organ protection are still not completely understood, basic as well as clinic researches on the mechanisms and applications of acupuncture and related techniques are being carried out.
Jing WangYou Wan
关键词:ACUPUNCTUREIMMUNOMODULATION
AQP1 is involved in glutamate induced nuclear swelling in astrocytes
Glutamate(Glu),the most important excitatory neurotransmitter in the central nervous systems(CNS),mediates syn...
Feng JIANGRui Chao CHAIAnn Yuen Kwan WONGChun Zhang YANGYe ZHOUAlbert Cheung Hoi YU
关键词:GLUTAMATEASTROCYTE
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DREAM in astrocyte regulates prodynorphin-dynorphin expression and may take part in chronic pain
Chronic pain,one of the most ancient and costly health problems,is poorly controlled and its underlying mechan...
Jiao-Hua JIANGAnn Yuen Kwan WONGJun-Hui WANGFeng-Bo SUNAlbert Cheung Hoi YU
关键词:ASTROCYTESDREAMPRODYNORPHINDYNORPHIN
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Association of ABCB1 Gene Polymorphisms with Efficacy and Adverse Reaction to Risperidone or Paliperidone in Han Chinese Schizophrenic Patients被引量:3
2016年
Dear editor, P-glycoprotein (P-gp, also known as ATP-binding cassette transport sub-family B member 1, ABCB1) is a potent ATP-dependent efflux pump for a wide variety of drugs. Although studies of its substrates are abundant [ 1, 2], and ABCB1 is a well-conserved gene, there is increasing evi- dence that its polymorphisms affect substrate specificity [3]. A previous study reported that the synonymous single nucleotide polymorphism (SNP) C3435T (rs1045642) affects the timing of co-translational folding and insertionof P-gp into the membrane,
Weifeng MiFeihu LiuYongqiao LiuBo DuWeidong XiaoLingzhi LiLan HuangTianlan LuJia HeLe ShiWeihua YueHongyan Zhang
Protein kinase D: a new player among the signaling proteins that regulate functions in the nervous system被引量:4
2014年
Protein kinase D (PKD) is an evolutionarily-conserved family of protein kinases. It has structural, regulatory, and enzymatic properties quite different from the PKC family. Many stimuli induce PKD signaling, including G-protein-coupled receptor agonists and growth factors. PKD1 is the most studied member of the family. It functions during cell proliferation, differentiation, secretion, cardiac hypertrophy, immune regulation, angiogenesis, and cancer. Previously, we found that PKD1 is also critically involved in pain modulation. Since then, a series of studies performed in our lab and by other groups have shown that PKDs also participate in other processes in the nervous system including neuronal polarity establishment, neuroprotection, and learning. Here, we discuss the connections between PKD structure, enzyme function, and localization, and summarize the recent findings on the roles of PKD-mediated signaling in the nervous system.
Gang LiYun Wang
关键词:PKDNEUROPROTECTION
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