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Synaptic potentiation of anterior cingulate cortex contributes to chronic pain of Parkinson's disease SCIE PubMed
期刊论文 | 2021 , 14 (1) | MOLECULAR BRAIN
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Abstract :

Parkinson's disease (PD) is a multi-system neurodegenerative disorder. Patients with PD often suffer chronic pain. In the present study, we investigated motor, sensory and emotional changes in three different PD mice models. We found that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treatment caused significant changes in all measurements. Mechanical hypersensitivity of PD model induced by MPTP peaked at 3 days and persisted for at least 14 days. Using Fos transgenic mice, we found that neurons in the anterior cingulate cortex (ACC) were activated after MPTP treatment. Inhibiting ACC by bilateral microinjection of muscimol significantly reduced mechanical hypersensitivity and anxiety-like responses. By contrast, MPTP induced motor deficit was not affected, indicating ACC activity is mostly responsible for sensory and emotional changes. We also investigated excitatory synaptic transmission and plasticity using brain slices of MPTP treated animals. While L-LTP was blocked or significantly reduced. E-LTP was not significantly affected in slices of MPTP treated animals. LTD induced by repetitive stimulation was not affected. Furthermore, we found that paired-pulse facilitation and spontaneous release of glutamate were also altered in MPTP treated animals, suggesting presynaptic enhancement of excitatory transmission in PD. Our results suggest that ACC synaptic transmission is enhanced in the animal model of PD, and cortical excitation may play important roles in PD related pain and anxiety.

Keyword :

ACC Parkinson's disease Chronic pain LTP MPTP

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GB/T 7714 Zhou, Zhaoxiang , Ye, Penghai , Li, Xu-Hui et al. Synaptic potentiation of anterior cingulate cortex contributes to chronic pain of Parkinson's disease [J]. | MOLECULAR BRAIN , 2021 , 14 (1) .
MLA Zhou, Zhaoxiang et al. "Synaptic potentiation of anterior cingulate cortex contributes to chronic pain of Parkinson's disease" . | MOLECULAR BRAIN 14 . 1 (2021) .
APA Zhou, Zhaoxiang , Ye, Penghai , Li, Xu-Hui , Zhang, Yuxiang , Li, Muhang , Chen, Qi-Yu et al. Synaptic potentiation of anterior cingulate cortex contributes to chronic pain of Parkinson's disease . | MOLECULAR BRAIN , 2021 , 14 (1) .
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Cortical mechanisms in migraine SCIE PubMed
期刊论文 | 2021 , 17 | MOLECULAR PAIN
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Migraine is the second most prevalent disorder in the world; yet, its underlying mechanisms are still poorly understood. Cumulative studies have revealed pivotal roles of cerebral cortex in the initiation, propagation, and termination of migraine attacks as well as the interictal phase. Investigation of basic mechanisms of the cortex in migraine not only brings insight into the underlying pathophysiology but also provides the basis for designing novel treatments. We aim to summarize the current research literatures and give a brief overview of the cortex and its role in migraine, including the basic structure and function; structural, functional, and biochemical neuroimaging; migraine-related genes; and theories related to cortex in migraine pathophysiology. We propose that long-term plasticity of synaptic transmission in the cortex encodes migraine.

Keyword :

long-term potentiation cerebral cortex migraine pathophysiology cortical spreading depression

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GB/T 7714 Dai, Wei , Liu, Ren-Hao , Qiu, Enchao et al. Cortical mechanisms in migraine [J]. | MOLECULAR PAIN , 2021 , 17 .
MLA Dai, Wei et al. "Cortical mechanisms in migraine" . | MOLECULAR PAIN 17 (2021) .
APA Dai, Wei , Liu, Ren-Hao , Qiu, Enchao , Liu, Yinglu , Chen, Zhiye , Chen, Xiaoyan et al. Cortical mechanisms in migraine . | MOLECULAR PAIN , 2021 , 17 .
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Brain-derived neurotrophic factor produced long-term synaptic enhancement in the anterior cingulate cortex of adult mice SCIE PubMed
期刊论文 | 2021 , 14 (1) | MOLECULAR BRAIN
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Previous studies have demonstrated that brain-derived neurotrophic factor (BDNF) is one of the diffusible messengers for enhancing synaptic transmission in the hippocampus. Less information is available about the possible roles of BDNF in the anterior cingulate cortex (ACC). In the present study, we used 64-electrode array field recording system to investigate the effect of BDNF on ACC excitatory transmission. We found that BDNF enhanced synaptic responses in a dose-dependent manner in the ACC in C57/BL6 mice. The enhancement was long-lasting, and persisted for at least 3 h. In addition to the enhancement, BDNF also recruited inactive synaptic responses in the ACC. Bath application of the tropomyosin receptor kinase B (TrkB) receptor antagonist K252a blocked BDNF-induced enhancement. L-type voltage-gated calcium channels (L-VGCC), metabotropic glutamate receptors (mGluRs), but not NMDA receptors were required for BDNF-produced enhancement. Moreover, calcium-stimulated adenylyl cyclase subtype 1 (AC1) but not AC8 was essential for the enhancement. A selective AC1 inhibitor NB001 completely blocked the enhancement. Furthermore, BDNF-produced enhancement occluded theta burst stimulation (TBS) induced long-term potentiation (LTP), suggesting that they may share similar signaling mechanisms. Finally, the expression of BDNF-induced enhancement depends on postsynaptic incorporation of calcium-permeable AMPA receptors (CP-AMPARs) and protein kinase M zeta (PKM zeta). Our results demonstrate that cortical BDNF may contribute to synaptic potentiation in the ACC.

Keyword :

Anterior cingulate cortex Adenylyl cyclase subtype 1 LTP AMPA Brain-derived neurotrophic factor

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GB/T 7714 Miao, Hui-Hui , Miao, Zhuang , Pan, Ji-Gang et al. Brain-derived neurotrophic factor produced long-term synaptic enhancement in the anterior cingulate cortex of adult mice [J]. | MOLECULAR BRAIN , 2021 , 14 (1) .
MLA Miao, Hui-Hui et al. "Brain-derived neurotrophic factor produced long-term synaptic enhancement in the anterior cingulate cortex of adult mice" . | MOLECULAR BRAIN 14 . 1 (2021) .
APA Miao, Hui-Hui , Miao, Zhuang , Pan, Ji-Gang , Li, Xu-Hui , Zhuo, Min . Brain-derived neurotrophic factor produced long-term synaptic enhancement in the anterior cingulate cortex of adult mice . | MOLECULAR BRAIN , 2021 , 14 (1) .
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Neuronal Adenylyl Cyclase Targeting Central Plasticity for the Treatment of Chronic Pain (vol 17, pg 861, 2020) SCIE PubMed
期刊论文 | 2021 , 18 (3) , 2129-2129 | NEUROTHERAPEUTICS
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GB/T 7714 Li, Xu-Hui , Chen, Qi-Yu , Zhuo, Min . Neuronal Adenylyl Cyclase Targeting Central Plasticity for the Treatment of Chronic Pain (vol 17, pg 861, 2020) [J]. | NEUROTHERAPEUTICS , 2021 , 18 (3) : 2129-2129 .
MLA Li, Xu-Hui et al. "Neuronal Adenylyl Cyclase Targeting Central Plasticity for the Treatment of Chronic Pain (vol 17, pg 861, 2020)" . | NEUROTHERAPEUTICS 18 . 3 (2021) : 2129-2129 .
APA Li, Xu-Hui , Chen, Qi-Yu , Zhuo, Min . Neuronal Adenylyl Cyclase Targeting Central Plasticity for the Treatment of Chronic Pain (vol 17, pg 861, 2020) . | NEUROTHERAPEUTICS , 2021 , 18 (3) , 2129-2129 .
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NMDA receptors and synaptic plasticity in the anterior cingulate cortex SCIE PubMed
期刊论文 | 2021 , 197 | NEUROPHARMACOLOGY
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The anterior cingulate cortex (ACC) plays an important role in pain modulation, and pain-related emotional disorders. In the ACC, two major forms of long-term potentiation (LTP) coexist in excitatory synapses and lay the basis of chronic pain and pain-related emotional disorders. The induction of postsynaptic LTP is dependent on the activation of postsynaptic NMDA receptors (NMDARs), while the presynaptic LTP is NMDAR-independent. Long-term depression (LTD) can also be divided into two types according to the degree of sensitivity to the inhibition of NMDARs. NMDAR heteromers containing GluN2A and GluN2B act as key molecules in both the NMDAR-dependent postsynaptic LTP and LTD. Additionally, NMDARs also exist in presynaptic terminals and modulate the evoked and spontaneous transmitter release. From a translational point of view, inhibiting subtypes of NMDARs and/or downstream signaling proteins may provide potential drug targets for chronic pain and its related emotional disorders. This article is part of the special Issue on 'Glutamate Receptors -NMDA receptors'.

Keyword :

NMDAR ACC pre-LTP post-LTP LTD

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GB/T 7714 Chen, Qi-Yu , Li, Xu-Hui , Zhuo, Min . NMDA receptors and synaptic plasticity in the anterior cingulate cortex [J]. | NEUROPHARMACOLOGY , 2021 , 197 .
MLA Chen, Qi-Yu et al. "NMDA receptors and synaptic plasticity in the anterior cingulate cortex" . | NEUROPHARMACOLOGY 197 (2021) .
APA Chen, Qi-Yu , Li, Xu-Hui , Zhuo, Min . NMDA receptors and synaptic plasticity in the anterior cingulate cortex . | NEUROPHARMACOLOGY , 2021 , 197 .
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Oxytocin in the anterior cingulate cortex attenuates neuropathic pain and emotional anxiety by inhibiting presynaptic long-term potentiation SCIE PubMed
期刊论文 | 2021 , 36 (3) | CELL REPORTS
WoS CC Cited Count: 2
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Oxytocin is a well-known neurohypophysial hormone that plays an important role in behavioral anxiety and nociception. Two major forms of long-term potentiation, presynaptic LTP (pre-LTP) and postsynaptic LTP (post-LTP), have been characterized in the anterior cingulate cortex (ACC). Both pre-LTP and post-LTP contribute to chronic-pain-related anxiety and behavioral sensitization. The roles of oxytocin in the ACC have not been studied. Here, we find that microinjections of oxytocin into the ACC attenuate nociceptive responses and anxiety-like behavioral responses in animals with neuropathic pain. Application of oxytocin selectively blocks the maintenance of pre-LTP but not post-LTP. In addition, oxytocin enhances inhibitory transmission and excites ACC interneurons. Similar results are obtained by using selective optical stimulation of oxytocin-containing projecting terminals in the ACC in animals with neuropathic pain. Our results demonstrate that oxytocin acts on central synapses and reduces chronic-pain-induced anxiety by reducing pre-LTP.

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GB/T 7714 Li, Xu-Hui , Matsuura, Takanori , Xue, Man et al. Oxytocin in the anterior cingulate cortex attenuates neuropathic pain and emotional anxiety by inhibiting presynaptic long-term potentiation [J]. | CELL REPORTS , 2021 , 36 (3) .
MLA Li, Xu-Hui et al. "Oxytocin in the anterior cingulate cortex attenuates neuropathic pain and emotional anxiety by inhibiting presynaptic long-term potentiation" . | CELL REPORTS 36 . 3 (2021) .
APA Li, Xu-Hui , Matsuura, Takanori , Xue, Man , Chen, Qi-Yu , Liu, Ren-Hao , Lu, Jing-Shan et al. Oxytocin in the anterior cingulate cortex attenuates neuropathic pain and emotional anxiety by inhibiting presynaptic long-term potentiation . | CELL REPORTS , 2021 , 36 (3) .
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Selective inhibition of adenylyl cyclase subtype 1 reduces inflammatory pain in chicken of gouty arthritis SCIE PubMed
期刊论文 | 2021 , 17 | MOLECULAR PAIN
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Lack of uricase leads to the high incidence of gout in humans and poultry, which is different from rodents. Therefore, chicken is considered to be one of the ideal animal models for the study of gout. Gout-related pain caused by the accumulation of urate in joints is one type of inflammatory pain, which causes damage to joint function. Our previous studies have demonstrated the crucial role of calcium-stimulated adenylyl cyclase subtype 1 (AC1) in inflammatory pain in rodents; however, there is no study in poultry. In the present study, we injected mono-sodium urate (MSU) into the left ankle joint of the chicken to establish a gouty arthritis model, and tested the effect of AC1 inhibitor NB001 on gouty arthritis in chickens. We found that MSU successfully induced spontaneous pain behaviors including sitting, standing on one leg, and limping after 1-3 h of injection into the left ankle of chickens. In addition, edema and mechanical pain hypersensitivity also occurred in the left ankle of chickens with gouty arthritis. After peroral administration of NB001 on chickens with gouty arthritis, both the spontaneous pain behaviors and the mechanical pain hypersensitivity were effectively relieved. The MSU-induced edema in the left ankle of chickens was not affected by NB001, suggesting a central effect of NB001. Our results provide a strong evidence that AC1 is involved in the regulation of inflammatory pain in poultry. A selective AC1 inhibitor NB001 produces an analgesic effect (not anti-inflammatory effect) on gouty pain and may be used for future treatment of gouty pain in both humans and poultry.

Keyword :

Gout chicken NB001 arthritis inflammatory pain adenylyl cyclase 1 spontaneous pain

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GB/T 7714 Liu, Ren-Hao , Shi, Wantong , Zhang, Yu-Xing et al. Selective inhibition of adenylyl cyclase subtype 1 reduces inflammatory pain in chicken of gouty arthritis [J]. | MOLECULAR PAIN , 2021 , 17 .
MLA Liu, Ren-Hao et al. "Selective inhibition of adenylyl cyclase subtype 1 reduces inflammatory pain in chicken of gouty arthritis" . | MOLECULAR PAIN 17 (2021) .
APA Liu, Ren-Hao , Shi, Wantong , Zhang, Yu-Xing , Zhuo, Min , Li, Xu-Hui . Selective inhibition of adenylyl cyclase subtype 1 reduces inflammatory pain in chicken of gouty arthritis . | MOLECULAR PAIN , 2021 , 17 .
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Multiple synaptic connections into a single cortical pyramidal cell or interneuron in the anterior cingulate cortex of adult mice SCIE PubMed
期刊论文 | 2021 , 14 (1) | MOLECULAR BRAIN
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The ACC is an important brain area for the processing of pain-related information. Studies of synaptic connections within the ACC provide an understanding of basic cellular and molecular mechanisms for brain functions such as pain, emotion and related cognitive functions. Previous study of ACC synaptic transmission mainly focused on presumably thalamic inputs into pyramidal cells. In the present study, we developed a new mapping technique by combining single neuron whole-cell patch-clamp recording with 64 multi-channel field potential recording (MED64) to examine the properties of excitatory inputs into a single neuron in the ACC. We found that a single patched pyramidal neuron or interneuron simultaneously received heterogeneous excitatory synaptic innervations from different subregions (ventral, dorsal, deep, and superficial layers) in the ACC. Conduction velocity is faster as stimulation distance increases in pyramidal neurons. Fast-spiking interneurons (FS-IN) show slower inactivation when compared to pyramidal neurons and regular-spiking interneurons (RS-IN) while pyramidal neurons displayed the most rapid activation. Bath application of non-competitive AMPA receptor antagonist GYKI 53655 followed by CNQX revealed that both FS-INs and RS-INs have AMPA and KA mediated components. Our studies provide a new strategy and technique for studying the network of synaptic connections.

Keyword :

Synaptic transmission Anterior cingulate cortex Heterogeneous excitatory input

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GB/T 7714 Lee, Jung-Hyun Alex , Miao, Zhuang , Chen, Qi-Yu et al. Multiple synaptic connections into a single cortical pyramidal cell or interneuron in the anterior cingulate cortex of adult mice [J]. | MOLECULAR BRAIN , 2021 , 14 (1) .
MLA Lee, Jung-Hyun Alex et al. "Multiple synaptic connections into a single cortical pyramidal cell or interneuron in the anterior cingulate cortex of adult mice" . | MOLECULAR BRAIN 14 . 1 (2021) .
APA Lee, Jung-Hyun Alex , Miao, Zhuang , Chen, Qi-Yu , Li, Xu-Hui , Zhuo, Min . Multiple synaptic connections into a single cortical pyramidal cell or interneuron in the anterior cingulate cortex of adult mice . | MOLECULAR BRAIN , 2021 , 14 (1) .
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NMDA GluN2C/2D receptors contribute to synaptic regulation and plasticity in the anterior cingulate cortex of adult mice SCIE PubMed
期刊论文 | 2021 , 14 (1) | MOLECULAR BRAIN
WoS CC Cited Count: 1
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Introduction N-Methyl-D-aspartate receptors (NMDARs) play a critical role in different forms of plasticity in the central nervous system. NMDARs are always assembled in tetrameric form, in which two GluN1 subunits and two GluN2 and/or GluN3 subunits combine together. Previous studies focused mainly on the hippocampus. The anterior cingulate cortex (ACC) is a key cortical region for sensory and emotional functions. NMDAR GluN2A and GluN2B subunits have been previously investigated, however much less is known about the GluN2C/2D subunits. Results In the present study, we found that the GluN2C/2D subunits are expressed in the pyramidal cells of ACC of adult mice. Application of a selective antagonist of GluN2C/2D, (2R*,3S*)-1-(9-bromophenanthrene-3-carbonyl) piperazine-2,3-dicarboxylic acid (UBP145), significantly reduced NMDAR-mediated currents, while synaptically evoked EPSCs were not affected. UBP145 affected neither the postsynaptic long-term potentiation (post-LTP) nor the presynaptic LTP (pre-LTP). Furthermore, the long-term depression (LTD) was also not affected by UBP145. Finally, both UBP145 decreased the frequency of the miniature EPSCs (mEPSCs) while the amplitude remained intact, suggesting that the GluN2C/2D may be involved in presynaptic regulation of spontaneous glutamate release. Conclusions Our results provide direct evidence that the GluN2C/2D contributes to evoked NMDAR mediated currents and mEPSCs in the ACC, which may have significant physiological implications.

Keyword :

LTP LTD GluN2C 2D ACC NMDAR

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GB/T 7714 Chen, Qi-Yu , Li, Xu-Hui , Lu, Jing-Shan et al. NMDA GluN2C/2D receptors contribute to synaptic regulation and plasticity in the anterior cingulate cortex of adult mice [J]. | MOLECULAR BRAIN , 2021 , 14 (1) .
MLA Chen, Qi-Yu et al. "NMDA GluN2C/2D receptors contribute to synaptic regulation and plasticity in the anterior cingulate cortex of adult mice" . | MOLECULAR BRAIN 14 . 1 (2021) .
APA Chen, Qi-Yu , Li, Xu-Hui , Lu, Jing-Shan , Liu, Yinglu , Lee, Jung-Hyun Alex , Chen, Yu-Xin et al. NMDA GluN2C/2D receptors contribute to synaptic regulation and plasticity in the anterior cingulate cortex of adult mice . | MOLECULAR BRAIN , 2021 , 14 (1) .
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Neuronal Adenylyl Cyclase Targeting Central Plasticity for the Treatment of Chronic Pain SCIE PubMed
期刊论文 | 2020 , 17 (3) , 861-873 | NEUROTHERAPEUTICS | IF: 7.62
WoS CC Cited Count: 8
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Abstract :

Chronic pain is a major health problem and the effective treatment for chronic pain is still lacking. The recent crisis created by the overuse of opioids for pain treatment has clearly shown the need for non-addictive novel pain medicine. Conventional pain medicines usually inhibit peripheral nociceptive transmission and reduce central transmission, especially pain-related excitatory transmission. For example, both opioids and gabapentin produce analgesic effects by inhibiting the release of excitatory transmitters and reducing neuronal excitability. Here, we will review recent studies of central synaptic plasticity contributing to central sensitization in chronic pain. Neuronal selective adenylyl cyclase subtype 1 (AC1) is proposed to be a key intracellular protein that causes both presynaptic and postsynaptic forms of long-term potentiation (LTP). Inhibiting the activity of AC1 by selective inhibitor NB001 blocks behavioral sensitization and injury-related anxiety in animal models of chronic pain. We propose that inhibiting injury-related LTPs will provide new mechanisms for designing novel medicines for the treatment of chronic pain and its related emotional disorders.

Keyword :

ACC Adenylyl cyclase subtype 1 Chronic pain NB001 Long-term potentiation

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GB/T 7714 Li, Xu-Hui , Chen, Qi-Yu , Zhuo, Min . Neuronal Adenylyl Cyclase Targeting Central Plasticity for the Treatment of Chronic Pain [J]. | NEUROTHERAPEUTICS , 2020 , 17 (3) : 861-873 .
MLA Li, Xu-Hui et al. "Neuronal Adenylyl Cyclase Targeting Central Plasticity for the Treatment of Chronic Pain" . | NEUROTHERAPEUTICS 17 . 3 (2020) : 861-873 .
APA Li, Xu-Hui , Chen, Qi-Yu , Zhuo, Min . Neuronal Adenylyl Cyclase Targeting Central Plasticity for the Treatment of Chronic Pain . | NEUROTHERAPEUTICS , 2020 , 17 (3) , 861-873 .
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