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Article: GluN2B-containing NMDARs in the mammalian brain: pharmacology, physiology, and pathology.

Ge, Yang / Wang, Yu Tian

2023 Volume 16, Page(s) 1190324

Abstract: Glutamate N-methyl-D-aspartate receptor (NMDAR) is critical for promoting physiological synaptic plasticity and neuronal viability. As a major subpopulation of the NMDAR, the GluN2B subunit-containing NMDARs have distinct pharmacological properties, ... ...

Abstract	Glutamate N-methyl-D-aspartate receptor (NMDAR) is critical for promoting physiological synaptic plasticity and neuronal viability. As a major subpopulation of the NMDAR, the GluN2B subunit-containing NMDARs have distinct pharmacological properties, physiological functions, and pathological relevance to neurological diseases compared with other NMDAR subtypes. In mature neurons, GluN2B-containing NMDARs are likely expressed as both diheteromeric and triheteromeric receptors, though the functional importance of each subpopulation has yet to be disentangled. Moreover, the C-terminal region of the GluN2B subunit forms structural complexes with multiple intracellular signaling proteins. These protein complexes play critical roles in both activity-dependent synaptic plasticity and neuronal survival and death signaling, thus serving as the molecular substrates underlying multiple physiological functions. Accordingly, dysregulation of GluN2B-containing NMDARs and/or their downstream signaling pathways has been implicated in neurological diseases, and various strategies to reverse these deficits have been investigated. In this article, we provide an overview of GluN2B-containing NMDAR pharmacology and its key physiological functions, highlighting the importance of this receptor subtype during both health and disease states.
Language	English
Publishing date	2023-05-31
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2452967-9
ISSN	1662-5099
ISSN	1662-5099
DOI	10.3389/fnmol.2023.1190324
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Article ; Online: Postsynaptic signaling at glutamatergic synapses as therapeutic targets.

Ge, Yang / Wang, Yu Tian

Current opinion in neurobiology

2022 Volume 75, Page(s) 102585

Abstract: Dysregulation of glutamatergic synapses plays an important role in the pathogenesis of neurological diseases. In addition to mediating excitatory synaptic transmission, postsynaptic glutamate receptors interact with various membrane and intracellular ... ...

Abstract	Dysregulation of glutamatergic synapses plays an important role in the pathogenesis of neurological diseases. In addition to mediating excitatory synaptic transmission, postsynaptic glutamate receptors interact with various membrane and intracellular proteins. They form structural and/or signaling synaptic protein complexes and thereby play diverse postsynaptic functions. Recently, several postsynaptic protein complexes have been associated with various neurological diseases and hence, have been characterized as important therapeutic targets. Moreover, novel small molecules and therapeutic peptides targeting and modulating the activities of these protein complexes have been discovered, some of which have advanced through preclinical translational research and/or clinical studies. This article describes the recent investigation of eight key protein complexes associated with the postsynaptic ionotropic and metabotropic glutamate receptors as therapeutic targets for central nervous system diseases.
MeSH term(s)	Receptors, Glutamate/metabolism ; Receptors, Metabotropic Glutamate/metabolism ; Synapses/physiology ; Synaptic Transmission/physiology
Chemical Substances	Receptors, Glutamate ; Receptors, Metabotropic Glutamate
Language	English
Publishing date	2022-06-20
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1078046-4
ISSN	1873-6882 ; 0959-4388
ISSN (online)	1873-6882
ISSN	0959-4388
DOI	10.1016/j.conb.2022.102585
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Zs.A 3260: Show issues

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Article ; Online: GluA1-homomeric AMPA receptor in synaptic plasticity and neurological diseases.

Ge, Yuan / Wang, Yu Tian

Neuropharmacology

2021 Volume 197, Page(s) 108708

Abstract: Synaptic transmission is one of the fundamental processes that all brain functions are based on. Changes in the strength of synaptic transmission among neurons are crucial for information processing in the central nervous system. The α-amino-3-hydroxy-5- ... ...

Abstract	Synaptic transmission is one of the fundamental processes that all brain functions are based on. Changes in the strength of synaptic transmission among neurons are crucial for information processing in the central nervous system. The α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid subtype of ionotropic glutamate receptors (AMPARs) mediate the majority of the fast excitatory synaptic transmission in the mammalian brain. Rapid trafficking of AMPARs in and out of the postsynaptic membrane is proposed to be a major mechanism for synaptic plasticity, and learning and memory. Defects in the regulated AMPAR trafficking have been shown to be involved in the pathogenesis of certain psychiatric and neurodegenerative diseases. Studies accumulated in the past 30 years have provided a detailed molecular insight on how the trafficking of AMPARs is modulated in a subunit-specific manner. In particular, emerging evidence supports that the regulated expression and trafficking of Ca
MeSH term(s)	Animals ; Humans ; Nervous System Diseases/genetics ; Nervous System Diseases/metabolism ; Nervous System Diseases/physiopathology ; Neuronal Plasticity/genetics ; Neuronal Plasticity/physiology ; Receptors, AMPA/genetics ; Receptors, AMPA/metabolism ; Receptors, AMPA/physiology ; Receptors, Ionotropic Glutamate/metabolism ; Synaptic Transmission
Chemical Substances	Receptors, AMPA ; Receptors, Ionotropic Glutamate ; glutamate receptor ionotropic, AMPA 1 (TFZ3H25BS1)
Language	English
Publishing date	2021-07-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	218272-5
ISSN	1873-7064 ; 0028-3908
ISSN (online)	1873-7064
ISSN	0028-3908
DOI	10.1016/j.neuropharm.2021.108708
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Article ; Online: scGCC: Graph Contrastive Clustering With Neighborhood Augmentations for scRNA-Seq Data Analysis.

Tian, Sheng-Wen / Ni, Jian-Cheng / Wang, Yu-Tian / Zheng, Chun-Hou / Ji, Cun-Mei

IEEE journal of biomedical and health informatics

2023 Volume 27, Issue 12, Page(s) 6133–6143

Abstract: Single-cell RNA sequencing (scRNA-seq) has rapidly emerged as a powerful technique for analyzing cellular heterogeneity at the individual cell level. In the analysis of scRNA-seq data, cell clustering is a critical step in downstream analysis, as it ... ...

Abstract	Single-cell RNA sequencing (scRNA-seq) has rapidly emerged as a powerful technique for analyzing cellular heterogeneity at the individual cell level. In the analysis of scRNA-seq data, cell clustering is a critical step in downstream analysis, as it enables the identification of cell types and the discovery of novel cell subtypes. However, the characteristics of scRNA-seq data, such as high dimensionality and sparsity, dropout events and batch effects, present significant computational challenges for clustering analysis. In this study, we propose scGCC, a novel graph self-supervised contrastive learning model, to address the challenges faced in scRNA-seq data analysis. scGCC comprises two main components: a representation learning module and a clustering module. The scRNA-seq data is first fed into a representation learning module for training, which is then used for data classification through a clustering module. scGCC can learn low-dimensional denoised embeddings, which is advantageous for our clustering task. We introduce Graph Attention Networks (GAT) for cell representation learning, which enables better feature extraction and improved clustering accuracy. Additionally, we propose five data augmentation methods to improve clustering performance by increasing data diversity and reducing overfitting. These methods enhance the robustness of clustering results. Our experimental study on 14 real-world datasets has demonstrated that our model achieves extraordinary accuracy and robustness. We also perform downstream tasks, including batch effect removal, trajectory inference, and marker genes analysis, to verify the biological effectiveness of our model.
MeSH term(s)	Humans ; Single-Cell Gene Expression Analysis ; Single-Cell Analysis/methods ; Cluster Analysis ; Data Analysis ; Gene Expression Profiling/methods ; Algorithms
Language	English
Publishing date	2023-12-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	2695320-1
ISSN	2168-2208 ; 2168-2194
ISSN (online)	2168-2208
ISSN	2168-2194
DOI	10.1109/JBHI.2023.3319551
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Zs.A 5483: Show issues

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Article ; Online: Getting "Ras"-ults: Solving Molecular Promiscuity through Microdomain-Selective Targeting.

Connor, Steven A / Wang, Yu Tian

Neuron

2018 Volume 98, Issue 4, Page(s) 675–678

Abstract: In this issue of Neuron, Zhang et al. (2018) report a powerful new method for probing subcellular microdomain-specific signaling in cellular function. Through a microdomain-targeting approach, they delineate how Ras-family GTPases balance signaling ... ...

Abstract	In this issue of Neuron, Zhang et al. (2018) report a powerful new method for probing subcellular microdomain-specific signaling in cellular function. Through a microdomain-targeting approach, they delineate how Ras-family GTPases balance signaling diversity with specificity required for various forms of hippocampal synaptic plasticity.
MeSH term(s)	Hippocampus ; Neuronal Plasticity ; Neurons ; Signal Transduction ; ras Proteins
Chemical Substances	ras Proteins (EC 3.6.5.2)
Language	English
Publishing date	2018-06-07
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	808167-0
ISSN	1097-4199 ; 0896-6273
ISSN (online)	1097-4199
ISSN	0896-6273
DOI	10.1016/j.neuron.2018.05.001
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Zs.A 2496: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 92: Show issues

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Article ; Online: Ketamine and its metabolite, (2R,6R)-HNK, restore hippocampal LTP and long-term spatial memory in the Wistar-Kyoto rat model of depression.

Aleksandrova, Lily R / Wang, Yu Tian / Phillips, Anthony G

Molecular brain

2020 Volume 13, Issue 1, Page(s) 92

Abstract: Accumulating evidence implicates dysregulation of hippocampal synaptic plasticity in the pathophysiology of depression. However, the effects of ketamine on synaptic plasticity and their contribution to its mechanism of action as an antidepressant, are ... ...

Abstract	Accumulating evidence implicates dysregulation of hippocampal synaptic plasticity in the pathophysiology of depression. However, the effects of ketamine on synaptic plasticity and their contribution to its mechanism of action as an antidepressant, are still unclear. We investigated ketamine's effects on in vivo dorsal hippocampal (dHPC) synaptic plasticity and their role in mediating aspects of antidepressant activity in the Wistar-Kyoto (WKY) model of depression. dHPC long-term potentiation (LTP) was significantly impaired in WKY rats compared to Wistar controls. Importantly, a single low dose (5 mg/kg, ip) of ketamine or its metabolite, (2R,6R)-HNK, rescued the LTP deficit in WKY rats at 3.5 h but not 30 min following injection, with residual effects at 24 h, indicating a delayed, sustained facilitatory effect on dHPC synaptic plasticity. Consistent with the observed dHPC LTP deficit, WKY rats exhibited impaired hippocampal-dependent long-term spatial memory as measured by the novel object location recognition test (NOLRT), which was effectively restored by pre-treatment with both ketamine or (2R,6R)-HNK. In contrast, in WKYs, which display abnormal stress coping, ketamine, but not (2R,6R)-HNK, had rapid and sustained effects in the forced swim test (FST), a commonly used preclinical screen for antidepressant-like activity. The differential effects of (2R,6R)-HNK observed here reveal a dissociation between drug effects on FST immobility and dHPC synaptic plasticity. Therefore, in the WKY rat model, restoring dHPC LTP was not correlated with ketamine's effects in FST, but importantly, may have contributed to the reversal of hippocampal-dependent cognitive deficits, which are critical features of clinical depression. Our findings support the theory that ketamine may reverse the stress-induced loss of connectivity in key neural circuits by engaging synaptic plasticity processes to "reset the system".
MeSH term(s)	Animals ; Depression/physiopathology ; Disease Models, Animal ; Hippocampus/physiopathology ; Immobilization ; Ketamine/analogs & derivatives ; Ketamine/metabolism ; Ketamine/pharmacology ; Long-Term Potentiation/drug effects ; Long-Term Potentiation/physiology ; Male ; Motor Activity/drug effects ; Open Field Test ; Rats, Inbred WKY ; Spatial Memory/drug effects ; Spatial Memory/physiology ; Stress, Psychological/complications ; Swimming ; Synaptic Transmission/drug effects
Chemical Substances	Ketamine (690G0D6V8H) ; 6-hydroxynorketamine (81395-70-2)
Language	English
Publishing date	2020-06-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2436057-0
ISSN	1756-6606 ; 1756-6606
ISSN (online)	1756-6606
ISSN	1756-6606
DOI	10.1186/s13041-020-00627-z
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Article ; Online: Corrigendum to "Evaluation of the Wistar-Kyoto rat model of depression and the role of synaptic plasticity in depression and antidepressant response" [Neurosci. Biobehav. Rev. 105 (2019) 1-23].

Aleksandrova, Lily R / Wang, Yu Tian / Phillips, Anthony G

Neuroscience and biobehavioral reviews

2020 Volume 116, Page(s) 162–163

Language	English
Publishing date	2020-07-01
Publishing country	United States
Document type	Published Erratum
ZDB-ID	282464-4
ISSN	1873-7528 ; 0149-7634
ISSN (online)	1873-7528
ISSN	0149-7634
DOI	10.1016/j.neubiorev.2020.05.011
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Zs.A 1371: Show issues

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Article ; Online: An Erbin Story: Amygdala Excitation-Inhibition Balance in Anxiety.

Aleksandrova, Lily R / Chen, Wenlin / Wang, Yu Tian

Biological psychiatry

2020 Volume 87, Issue 10, Page(s) 872–874

MeSH term(s)	Amygdala ; Anxiety ; Neurons ; Parvalbumins
Chemical Substances	Parvalbumins
Language	English
Publishing date	2020-05-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	209434-4
ISSN	1873-2402 ; 0006-3223
ISSN (online)	1873-2402
ISSN	0006-3223
DOI	10.1016/j.biopsych.2020.03.005
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Article ; Online: A New Method Based on Matrix Completion and Non-Negative Matrix Factorization for Predicting Disease-Associated miRNAs.

Gao, Zhen / Wang, Yu-Tian / Wu, Qing-Wen / Li, Lei / Ni, Jian-Cheng / Zheng, Chun-Hou

IEEE/ACM transactions on computational biology and bioinformatics

2022 Volume 19, Issue 2, Page(s) 763–772

Abstract: Numerous studies have shown that microRNAs are associated with the occurrence and development of human diseases. Thus, studying disease-associated miRNAs is significantly valuable to the prevention, diagnosis and treatment of diseases. In this paper, we ... ...

Abstract	Numerous studies have shown that microRNAs are associated with the occurrence and development of human diseases. Thus, studying disease-associated miRNAs is significantly valuable to the prevention, diagnosis and treatment of diseases. In this paper, we proposed a novel method based on matrix completion and non-negative matrix factorization (MCNMF)for predicting disease-associated miRNAs. Due to the information inadequacy on miRNA similarities and disease similarities, we calculated the latter via two models, and introduced the Gaussian interaction profile kernel similarity. In addition, the matrix completion (MC)was employed to further replenish the miRNA and disease similarities to improve the prediction performance. And to reduce the sparsity of miRNA-disease association matrix, the method of weighted K nearest neighbor (WKNKN)was used, which is a pre-processing step. We also utilized non-negative matrix factorization (NMF)using dual L
MeSH term(s)	Algorithms ; Computational Biology/methods ; Humans ; MicroRNAs/genetics
Chemical Substances	MicroRNAs
Language	English
Publishing date	2022-04-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1557-9964
ISSN (online)	1557-9964
DOI	10.1109/TCBB.2020.3027444
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Article ; Online: Allosteric potentiation of GABA

Chan, Elizabeth S / Ge, Yang / So, Yee Wah / Bai, Yun-Fei / Liu, Lidong / Wang, Yu Tian

Cell reports

2022 Volume 41, Issue 5, Page(s) 111584

Abstract: As the principal receptor that mediates both synaptic and tonic inhibition of neurons in the brain, the A-type gamma-aminobutyric acid receptor ( ... ...

Abstract	As the principal receptor that mediates both synaptic and tonic inhibition of neurons in the brain, the A-type gamma-aminobutyric acid receptor (GABA
MeSH term(s)	Receptors, GABA-A/metabolism ; Netrin-1/metabolism ; Neurons/metabolism ; gamma-Aminobutyric Acid/metabolism ; Homeostasis
Chemical Substances	Receptors, GABA-A ; Netrin-1 (158651-98-0) ; gamma-Aminobutyric Acid (56-12-2)
Language	English
Publishing date	2022-10-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2022.111584
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