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Article ; Online: Selective enhancement of fear extinction by inhibiting neuronal adenylyl cyclase 1 (AC1) in aged mice.

Shi, Wantong / Chen, Qi-Yu / Ma, Yujie / Wan, Jinjin / Li, Xu-Hui / Zhuo, Min

2024 Volume 17, Issue 1, Page(s) 11

Abstract: Adenylyl cyclase 1 (AC1) is a selective subtype of ACs, which is selectively expressed in neurons. The activation of AC1 is activity-dependent, and AC1 plays an important role in cortical excitation that contributes to chronic pain and related emotional ... ...

Abstract	Adenylyl cyclase 1 (AC1) is a selective subtype of ACs, which is selectively expressed in neurons. The activation of AC1 is activity-dependent, and AC1 plays an important role in cortical excitation that contributes to chronic pain and related emotional disorders. Previous studies have reported that human-used NB001 (hNB001, a selective AC1 inhibitor) produced analgesic effects in different animal models of chronic pain. However, the potential effects of hNB001 on learning and memory have been less investigated. In the present study, we found that hNB001 affected neither the induction nor the expression of trace fear, but selectively enhanced the relearning ability during the extinction in aged mice. By contrast, the same application of hNB001 did not affect recent, remote auditory fear memory, or remote fear extinction in either adult or aged mice. Furthermore, a single or consecutive 30-day oral administration of hNB001 did not affect acute nociceptive response, motor function, or anxiety-like behavior in either adult or aged mice. Our results are consistent with previous findings that inhibition of AC1 did not affect general sensory, emotional, and motor functions in adult mice, and provide strong evidence that inhibiting the activity of AC1 may be beneficial for certain forms of learning and memory in aged mice.
MeSH term(s)	Humans ; Mice ; Animals ; Fear/physiology ; Chronic Pain ; Extinction, Psychological ; Adenylyl Cyclases/metabolism ; Neurons/metabolism
Chemical Substances	adenylyl cyclase 1 (EC 4.6.1.1) ; Adenylyl Cyclases (EC 4.6.1.1)
Language	English
Publishing date	2024-02-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2436057-0
ISSN	1756-6606 ; 1756-6606
ISSN (online)	1756-6606
ISSN	1756-6606
DOI	10.1186/s13041-024-01083-9
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Multiple modulatory roles of serotonin in chronic pain and injury-related anxiety.

Hao, Shun / Shi, Wantong / Liu, Weiqi / Chen, Qi-Yu / Zhuo, Min

Frontiers in synaptic neuroscience

2023 Volume 15, Page(s) 1122381

Abstract: Chronic pain is long-lasting pain that often persists during chronic diseases or after recovery from disease or injury. It often causes serious side effects, such as insomnia, anxiety, or depression which negatively impacts the patient's overall quality ... ...

Abstract	Chronic pain is long-lasting pain that often persists during chronic diseases or after recovery from disease or injury. It often causes serious side effects, such as insomnia, anxiety, or depression which negatively impacts the patient's overall quality of life. Serotonin (5-HT) in the central nervous system (CNS) has been recognized as an important neurotransmitter and neuromodulator which regulates various physiological functions, such as pain sensation, cognition, and emotions-especially anxiety and depression. Its widespread and diverse receptors underlie the functional complexity of 5-HT in the CNS. Recent studies found that both chronic pain and anxiety are associated with synaptic plasticity in the anterior cingulate cortex (ACC), the insular cortex (IC), and the spinal cord. 5-HT exerts multiple modulations of synaptic transmission and plasticity in the ACC and the spinal cord, including activation, inhibition, and biphasic actions. In this review, we will discuss the multiple actions of the 5-HT system in both chronic pain and injury-related anxiety, and the synaptic mechanisms behind them. It is likely that the specific 5-HT receptors would be new promising therapeutic targets for the effective treatment of chronic pain and injury-related anxiety in the future.
Language	English
Publishing date	2023-04-18
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2592086-8
ISSN	1663-3563
ISSN	1663-3563
DOI	10.3389/fnsyn.2023.1122381
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Article ; Online: Selective inhibition of adenylyl cyclase subtype 1 reduces inflammatory pain in chicken of gouty arthritis.

Liu, Ren-Hao / Shi, Wantong / Zhang, Yu-Xiang / Zhuo, Min / Li, Xu-Hui

Molecular pain

2022 Volume 17, Page(s) 17448069211047863

Abstract: 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 ...

Abstract	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.
MeSH term(s)	Adenylyl Cyclases ; Animals ; Arthritis, Gouty/complications ; Arthritis, Gouty/drug therapy ; Chickens ; Pain/complications ; Pain/drug therapy ; Uric Acid
Chemical Substances	Uric Acid (268B43MJ25) ; Adenylyl Cyclases (EC 4.6.1.1)
Language	English
Publishing date	2022-01-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2174252-2
ISSN	1744-8069 ; 1744-8069
ISSN (online)	1744-8069
ISSN	1744-8069
DOI	10.1177/17448069211047863
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Article ; Online: Activation of the glutamatergic cingulate cortical-cortical connection facilitates pain in adult mice.

Li, Xu-Hui / Shi, Wantong / Chen, Qi-Yu / Hao, Shun / Miao, Hui-Hui / Miao, Zhuang / Xu, Fang / Bi, Guo-Qiang / Zhuo, Min

Communications biology

2023 Volume 6, Issue 1, Page(s) 1247

Abstract: The brain consists of the left and right cerebral hemispheres and both are connected by callosal projections. Less is known about the basic mechanism of this cortical-cortical connection and its functional importance. Here we investigate the cortical- ... ...

Abstract	The brain consists of the left and right cerebral hemispheres and both are connected by callosal projections. Less is known about the basic mechanism of this cortical-cortical connection and its functional importance. Here we investigate the cortical-cortical connection between the bilateral anterior cingulate cortex (ACC) by using the classic electrophysiological and optogenetic approach. We find that there is a direct synaptic projection from one side ACC to the contralateral ACC. Glutamate is the major excitatory transmitter for bilateral ACC connection, including projections to pyramidal cells in superficial (II/III) and deep (V/VI) layers of the ACC. Both AMPA and kainate receptors contribute to synaptic transmission. Repetitive stimulation of the projection also evoked postsynaptic Ca
MeSH term(s)	Mice ; Animals ; Gyrus Cinguli/physiology ; Synaptic Transmission/physiology ; Neuralgia ; Pyramidal Cells ; Glutamic Acid
Chemical Substances	Glutamic Acid (3KX376GY7L)
Language	English
Publishing date	2023-12-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2399-3642
ISSN (online)	2399-3642
DOI	10.1038/s42003-023-05589-1
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Article ; Online: Inhibition of calcium-stimulated adenylyl cyclase subtype 1 (AC1) for the treatment of neuropathic and inflammatory pain in adult female mice.

Zhou, Zhaoxiang / Shi, Wantong / Fan, Kexin / Xue, Man / Zhou, Sibo / Chen, Qi-Yu / Lu, Jing-Shan / Li, Xu-Hui / Zhuo, Min

Molecular pain

2021 Volume 17, Page(s) 17448069211021698

Abstract: Cortical long-term potentiation (LTP) serves as a cellular model for chronic pain. As an important subtype of adenylyl cyclases (ACs), adenylyl cyclase subtype 1 (AC1) is critical for the induction of cortical LTP in the anterior cingulate cortex (ACC). ... ...

Abstract	Cortical long-term potentiation (LTP) serves as a cellular model for chronic pain. As an important subtype of adenylyl cyclases (ACs), adenylyl cyclase subtype 1 (AC1) is critical for the induction of cortical LTP in the anterior cingulate cortex (ACC). Genetic deletion of AC1 or pharmacological inhibition of AC1 blocked behavioral allodynia in animal models of neuropathic and inflammatory pain. Our previous experiments have identified a lead candidate AC1 inhibitor, NB001, which is highly selective for AC1 over other AC isoforms, and found that NB001 is effective in inhibiting behavioral allodynia in animal models of chronic neuropathic and inflammatory pain. However, previous experiments were carried out in adult male animals. Considering the potential gender difference as an important issue in researches of pain and analgesia, we investigated the effect of NB001 in female chronic pain animal models. We found that NB001, when administered orally, has an analgesic effect in female animal models of neuropathic and inflammatory pain without any observable side effect. Genetic deletion of AC1 also reduced allodynia responses in models of neuropathic pain and chronic inflammation pain in adult female mice. In brain slices of adult female mice, bath application of NB001(20 μM) blocked the induction of LTP in ACC. Our results indicate that calcium-stimulated AC1 is required for injury-related cortical LTP and behavioral allodynia in both sexes of adult animals, and NB001 can be used as a potential therapeutic drug for treating neuropathic and inflammatory pain in man and woman.
MeSH term(s)	Adenylyl Cyclases/genetics ; Adenylyl Cyclases/metabolism ; Animals ; Calcium ; Female ; Gyrus Cinguli/metabolism ; Humans ; Long-Term Potentiation ; Male ; Mice ; Neuralgia/drug therapy
Chemical Substances	Adenylyl Cyclases (EC 4.6.1.1) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2021-06-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2174252-2
ISSN	1744-8069 ; 1744-8069
ISSN (online)	1744-8069
ISSN	1744-8069
DOI	10.1177/17448069211021698
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Article ; Online: Reduced behavioral withdrawal responses during fear retrieval in adult mice and rats.

Zhou, Zhaoxiang / Fan, Kexin / Shi, Wantong / Chen, Qiyu / Zhuo, Min / Lu, Jingshan

Molecular pain

2019 Volume 15, Page(s) 1744806919876157

MeSH term(s)	Animals ; Anxiety/physiopathology ; Behavior, Animal/physiology ; Fear ; Female ; Male ; Mice ; Models, Animal ; Pain Threshold/physiology ; Rats
Language	English
Publishing date	2019-08-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2174252-2
ISSN	1744-8069 ; 1744-8069
ISSN (online)	1744-8069
ISSN	1744-8069
DOI	10.1177/1744806919876157
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Article ; Online: Inhibiting neuronal AC1 for treating anxiety and headache in the animal model of migraine.

Liu, Ren-Hao / Zhang, Mingjie / Xue, Man / Wang, Tao / Lu, Jing-Shan / Li, Xu-Hui / Chen, Yu-Xin / Fan, Kexin / Shi, Wantong / Zhou, Si-Bo / Chen, Qi-Yu / Kang, Li / Song, Qian / Yu, Shengyuan / Zhuo, Min

iScience

2023 Volume 26, Issue 6, Page(s) 106790

Abstract: Migraines are a common medical condition. From a basic science point of view, the central mechanism for migraine and headache is largely unknown. In the present study, we demonstrate that cortical excitatory transmission is significantly enhanced in the ... ...

Abstract	Migraines are a common medical condition. From a basic science point of view, the central mechanism for migraine and headache is largely unknown. In the present study, we demonstrate that cortical excitatory transmission is significantly enhanced in the anterior cingulate cortex (ACC)-a brain region which is critical for pain perception. Biochemical studies found that the phosphorylation levels of both the NMDA receptor GluN2B and AMPA receptor GluA1 were enhanced in ACC of migraine rats. Both the presynaptic release of glutamate and postsynaptic responses of AMPA receptors and NMDA receptors were enhanced. Synaptic long-term potentiation (LTP) was occluded. Furthermore, behavioral anxiety and nociceptive responses were increased, which were reversed by application of AC1 inhibitor NB001 within ACC. Our results provide strong evidence that cortical LTPs contribute to migraine-related pain and anxiety. Drugs that inhibit cortical excitation such as NB001 may serve as potential medicines for treating migraine in the future.
Language	English
Publishing date	2023-04-28
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.106790
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Article ; Online: Enhancement of behavioral nociceptive responses but not itching responses by viewing mirror images in adult mice.

Zhou, Si-Bo / Xue, Man / Shi, Wantong / Fan, Kexin / Chen, Yu-Xin / Chen, Qi-Yu / Wang, Jinjun / Lu, Jing-Shan / Li, Xu-Hui / Zhuo, Min

Molecular pain

2022 Volume 18, Page(s) 17448069221111158

Abstract: Can mice recognize themselves in a mirror? The answer is unclear. Previous studies have reported that adult mice - when shown itch-like videos - demonstrated itch empathy. However, this was proven to be unreproducible in other studies. In the present ... ...

Abstract	Can mice recognize themselves in a mirror? The answer is unclear. Previous studies have reported that adult mice - when shown itch-like videos - demonstrated itch empathy. However, this was proven to be unreproducible in other studies. In the present study, we wanted to examine whether adult mice were able to recognize their mirror image. In our testing, we found that mice spent more time in the central area in an open field with mirrors surrounding the chamber than those in a normal open field. In a similar open field test with four mice placed in four directions, mice showed similar behavioral responses to those with mirrors. These results indicate that mice are able to recognize images in the mirror, however, they cannot distinguish their own mirror images from the mirror images of other mice. To repeat the experiments of itch empathy, we compared the itch responses of mice in the mirrored environment, to those without. No significant difference in itching responses was detected. Differently, in the case of chemical pain (formalin injection), animals' nociceptive responses to formalin during Phase II were significantly enhanced in the mirrored open field. A new format of heat map was developed to help the analysis of the trace of mice in the open field. Our results suggest that mice do recognize the presence of mice in the mirror, and their nociceptive - but not itch - responses are enhanced.
MeSH term(s)	Animals ; Behavior, Animal ; Formaldehyde ; Mice ; Nociception ; Pain ; Pruritus
Chemical Substances	Formaldehyde (1HG84L3525)
Language	English
Publishing date	2022-06-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2174252-2
ISSN	1744-8069 ; 1744-8069
ISSN (online)	1744-8069
ISSN	1744-8069
DOI	10.1177/17448069221111158
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Article ; Online: Correction to: Synaptic potentiation of anterior cingulate cortex contributes to chronic pain of Parkinson's disease.

Zhou, Zhaoxiang / Ye, Penghai / Li, Xu-Hui / Zhang, Yuxiang / Li, Muhang / Chen, Qi-Yu / Lu, Jing-Shan / Xue, Man / Li, Yanan / Liu, Weiqi / Lu, Lin / Shi, Wantong / Xu, Ping-Yi / Zhuo, Min

Molecular brain

2022 Volume 15, Issue 1, Page(s) 58

Language	English
Publishing date	2022-06-22
Publishing country	England
Document type	Published Erratum
ZDB-ID	2436057-0
ISSN	1756-6606 ; 1756-6606
ISSN (online)	1756-6606
ISSN	1756-6606
DOI	10.1186/s13041-022-00943-6
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Article ; Online: Whole-brain mapping of efferent projections of the anterior cingulate cortex in adult male mice.

Shi, Wantong / Xue, Man / Wu, Fengyi / Fan, Kexin / Chen, Qi-Yu / Xu, Fang / Li, Xu-Hui / Bi, Guo-Qiang / Lu, Jing-Shan / Zhuo, Min

Molecular pain

2022 Volume 18, Page(s) 17448069221094529

Abstract: The anterior cingulate cortex (ACC) is a key cortical region that plays an important role in pain perception and emotional functions. Previous studies of the ACC projections have been collected primarily from monkeys, rabbits and rats. Due to ... ...

Abstract	The anterior cingulate cortex (ACC) is a key cortical region that plays an important role in pain perception and emotional functions. Previous studies of the ACC projections have been collected primarily from monkeys, rabbits and rats. Due to technological advances, such as gene manipulation, recent progress has been made in our understanding of the molecular and cellular mechanisms of the ACC-related chronic pain and emotion is mainly obtained from adult mice. Few anatomic studies have examined the whole-brain projections of the ACC in adult mice. In the present study, we examined the continuous axonal outputs of the ACC in the whole brain of adult male mice. We used the virus anterograde tracing technique and an ultrahigh-speed imaging method of Volumetric Imaging with Synchronized on-the-fly-scan and Readout (VISoR). We created a three-dimensional (3D) reconstruction of mouse brains. We found that the ACC projected ipsilaterally primarily to the caudate putamen (CPu), ventral thalamic nucleus, zona incerta (ZI), periaqueductal gray (PAG), superior colliculus (SC), interpolar spinal trigeminal nucleus (Sp5I), and dorsal medullary reticular nucleus (MdD). The ACC also projected to contralateral brain regions, including the ACC, reuniens thalamic nucleus (Re), PAG, Sp5I, and MdD. Our results provide a whole-brain mapping of efferent projections from the ACC in adult male mice, and these findings are critical for future studies of the molecular and synaptic mechanisms of the ACC and its related network in mouse models of brain diseases.
MeSH term(s)	Animals ; Brain ; Brain Mapping ; Efferent Pathways ; Gyrus Cinguli ; Male ; Mice ; Periaqueductal Gray ; Rabbits ; Rats ; Trigeminal Nucleus, Spinal
Language	English
Publishing date	2022-03-31
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2174252-2
ISSN	1744-8069 ; 1744-8069
ISSN (online)	1744-8069
ISSN	1744-8069
DOI	10.1177/17448069221094529
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