Advances in neurobiology最新文献_第3页

Electrophysiological Methods to Explore the Function of Monoamine Transporters. 探索单胺转运蛋白功能的电生理方法。

Advances in neurobiology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-96364-3_6

Danila Boytsov, Michael Freissmuth, Walter Sandtner

{"title":"Electrophysiological Methods to Explore the Function of Monoamine Transporters.","authors":"Danila Boytsov, Michael Freissmuth, Walter Sandtner","doi":"10.1007/978-3-031-96364-3_6","DOIUrl":"https://doi.org/10.1007/978-3-031-96364-3_6","url":null,"abstract":"In this chapter we will show how electrophysiological recordings were used to gain insights into the transport kinetics and pharmacology of monoamine transporters (MATs). We will discuss data obtained from whole cell patch clamp recordings that allow for real time monitoring of MAT function. A notable property of MATs is that they carry so-called uncoupled currents. We will begin this chapter by reviewing the experimental evidence that has led to the conclusion that the currents carried by MATs are largely uncoupled and, therefore, not directly related to substrate transport. We will discuss how this has made it difficult to understand the operation of MATs. We will also explain why the existence of these currents has led to the proposition that MATs do not operate by alternate access but rather by a single file diffusion mechanism. However, we will show that ultimately the uncoupled currents carried by MATs can be most parsimoniously explained within the framework of the alternate access mechanism. We will review the existing evidence that MATs, like most other transporters, undergo a cycle during which they visit outward and inward-facing conformations (i.e., the transport cycle). We will outline what we have learned about the transport cycle of MATs from electrophysiological recordings. Thereafter, we will describe how electrophysiological recordings can be utilized to understand how drugs that target MATs affect their operation. To this end, we will discuss the binding modes of three different MAT ligands: (i) amphetamines, (ii) ibogaine, and (iii) zinc.","PeriodicalId":7360,"journal":{"name":"Advances in neurobiology","volume":"46 ","pages":"143-162"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unlocking the Potential of High-Quality Dopamine Transporter Pharmacological Data: Advancing Robust Machine Learning-Based QSAR Modeling. 解锁高质量多巴胺转运体药理学数据的潜力：推进基于机器学习的强大QSAR建模。

Advances in neurobiology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-96364-3_3

Kuo Hao Lee, Sung Joon Won, Precious Oyinloye, Lei Shi

{"title":"Unlocking the Potential of High-Quality Dopamine Transporter Pharmacological Data: Advancing Robust Machine Learning-Based QSAR Modeling.","authors":"Kuo Hao Lee, Sung Joon Won, Precious Oyinloye, Lei Shi","doi":"10.1007/978-3-031-96364-3_3","DOIUrl":"https://doi.org/10.1007/978-3-031-96364-3_3","url":null,"abstract":"The dopamine transporter (DAT) plays a critical role in the central nervous system and has been implicated in numerous psychiatric disorders. The ligand-based approaches are instrumental to decipher the structure-activity relationship (SAR) of DAT ligands, especially the quantitative SAR (QSAR) modeling. By gathering and analyzing data from literature and databases, we systematically assemble a diverse range of ligands binding to DAT, aiming to discern the general features of DAT ligands and uncover the chemical space for potential novel DAT ligand scaffolds. The aggregation of DAT pharmacological activity data, particularly from databases like ChEMBL, provides a foundation for constructing robust QSAR models. The compilation and meticulous filtering of these data, establishing high-quality training data sets with specific divisions of pharmacological assays and data types, along with the application of QSAR modeling, prove to be a promising strategy for navigating the pertinent chemical space. Through a systematic comparison of DAT QSAR models using training data sets from various ChEMBL releases, we underscore the positive impact of enhanced data set quality and increased data set size on the predictive power of DAT QSAR models.","PeriodicalId":7360,"journal":{"name":"Advances in neurobiology","volume":"46 ","pages":"63-94"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Oligodendroglia and Myelin: Supporting the Connectome. 少突胶质细胞和髓磷脂：支持连接组。

Advances in neurobiology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-87919-7_1

Jianqin Niu, Alexei Verkhratsky, Arthur Butt, Chenju Yi

{"title":"Oligodendroglia and Myelin: Supporting the Connectome.","authors":"Jianqin Niu, Alexei Verkhratsky, Arthur Butt, Chenju Yi","doi":"10.1007/978-3-031-87919-7_1","DOIUrl":"https://doi.org/10.1007/978-3-031-87919-7_1","url":null,"abstract":"Oligodendroglia are the only cell lineage of the central nervous system (CNS) responsible for producing myelin. They originate from precursor cells known as oligodendrocyte precursor cells (OPCs), which are born around the ventricular zones of the brain and spinal cord and migrate throughout the developing CNS, and many of them ultimately differentiate into mature myelinating oligodendrocytes. Recent research has shown that OPCs and oligodendrocytes possess distinct characteristics when compared either to other types of glial cells in the CNS or to each other. Under different physiological and pathophysiological conditions, the processes of development or regeneration, the features, and, in some cases, even the functions of oligodendroglia can be modified. These changes can contribute to disease progression and affect the functional status of the nervous system. For instance, experience-dependent \"adaptive\" myelination plays a crucial role in the plasticity of neuronal circuits and influences learning processes; additionally, the non-myelinating functions of oligodendroglia expand their pathological potential, allowing them to regulate neuronal development and activity, angiogenesis, astrocyte maturation, and neuroinflammation. This chapter serves as a comprehensive introduction to oligodendroglia by presenting evidence from fundamental studies and fresh insights into their development, physiological and pathophysiological attributes, as well as the newly discovered non-myelinating functions.","PeriodicalId":7360,"journal":{"name":"Advances in neurobiology","volume":"43 ","pages":"1-37"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Causal Mechanisms of Monoamine Transporter Phosphorylation. 单胺转运蛋白磷酸化的致病机制。

Advances in neurobiology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-96364-3_5

Sammanda Ramamoorthy, Durairaj Ragu Varman, Lankupalle D Jayanthi

{"title":"Causal Mechanisms of Monoamine Transporter Phosphorylation.","authors":"Sammanda Ramamoorthy, Durairaj Ragu Varman, Lankupalle D Jayanthi","doi":"10.1007/978-3-031-96364-3_5","DOIUrl":"https://doi.org/10.1007/978-3-031-96364-3_5","url":null,"abstract":"Monoamine transporters are essential proteins located at presynaptic terminals that play a crucial role in regulating neurotransmission of serotonin, dopamine, and norepinephrine by rapid reuptake of released amines from the synapse. Clinically used antidepressants and widely abused psychostimulants exhibit a high affinity for amine transporters. Function and expression of biogenic amine transporter are altered in subjects suffering from psychiatric diseases such as depression and in psychostimulant use disorder. Therefore, proper functional regulation of monoamine transporters is critical in maintaining normal amine homeostasis. Monoamine transporters possess several potential phosphorylation sites/motifs and exist in a phosphorylated state. Various cellular protein kinases and phosphatases are known to regulate the phosphorylation dynamics of amine transporters, which in turn influences subcellular expression and trafficking, microdomain-specific protein-protein interactions, transporter protein degradation, and overall transport capacity. Dysfunctional amine transporter function, phosphorylation, and association with interacting proteins are evident in neuropsychiatric disease states, including psychostimulant use disorder. However, the neurobiological consequences of in vivo amine transporter phosphorylation and its regulation remain unclear. Recent studies utilizing intact animal models are beginning to connect these molecular mechanisms with observed animal behaviors. This review summarizes current knowledge on the causal role of amine transporter phosphorylation in regulating amine transport and its relevance to animal behavior. Further understanding of phosphorylation-dependent molecular mechanisms governing amine transporter regulation potentially identifies regulatory motif(s) as potential therapeutic targets for treating neuropsychiatric disorders.","PeriodicalId":7360,"journal":{"name":"Advances in neurobiology","volume":"46 ","pages":"121-142"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dopamine-Glutamate and Dopamine-GABA Co-release. 多巴胺-谷氨酸和多巴胺- gaba共释放。

Advances in neurobiology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-96364-3_8

Annalisa Scimemi

引用次数: 0

Monoamine Transporters in Drugs of Abuse: Insights from Fast Scan Cyclic Voltammetry. 滥用药物中的单胺转运体：快速扫描循环伏安法的见解。

Advances in neurobiology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-96364-3_7

Shanna B Samels, Pelin Yuksel, Rodrigo A España

{"title":"Monoamine Transporters in Drugs of Abuse: Insights from Fast Scan Cyclic Voltammetry.","authors":"Shanna B Samels, Pelin Yuksel, Rodrigo A España","doi":"10.1007/978-3-031-96364-3_7","DOIUrl":"https://doi.org/10.1007/978-3-031-96364-3_7","url":null,"abstract":"Monoamine transmission is critical for regulating numerous physiological processes, including stress, learning, motor activity, and reward. Over the past few decades, the adoption of fast scan cyclic voltammetry has unveiled an intricate interplay between monoamine release and uptake dynamics, particularly concerning monoamine transporter involvement in reward and reinforcement processes for drugs of abuse. This review discusses how fast scan cyclic voltammetry has revolutionized our understanding of the processes that govern monoamine release and uptake, emphasizing the heterogeneity in transporter function across terminal regions, the influence of autoreceptors on monoamine transmission, and the complex interactions between drugs of abuse and monoamine transporters. While much of the review focuses on what is known about dopamine transporters-due to the wealth of evidence on dopamine transmission-we also emphasize significant gaps in knowledge regarding the serotonin and norepinephrine transporters. Finally, we highlight remaining questions about the dynamic nature of monoaminergic transporter efficiency and suggest new areas of investigation to gain a more comprehensive understanding of the biochemical mechanisms through which monoamine transporters regulate behavior.","PeriodicalId":7360,"journal":{"name":"Advances in neurobiology","volume":"46 ","pages":"163-196"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Effects of Exercise on Hippocampus-Based Cognitive Dysfunction in Type 2 Diabetes Mellitus: A Possible Involvement of Hippocampal Monocarboxylate Transporter 2. 运动对2型糖尿病海马认知功能障碍的影响：海马单羧酸转运蛋白2的可能参与

Advances in neurobiology Pub Date : 2025-01-01 DOI: 10.1007/978-981-95-0066-6_15

Takeru Shima, Hideaki Soya

引用次数: 0

Exercise as a Therapeutic Intervention for Alzheimer's Disease. 运动作为阿尔茨海默病的治疗干预。

Advances in neurobiology Pub Date : 2025-01-01 DOI: 10.1007/978-981-95-0066-6_16

Dong-Joo Hwang, Joon-Yong Cho

{"title":"Exercise as a Therapeutic Intervention for Alzheimer's Disease.","authors":"Dong-Joo Hwang, Joon-Yong Cho","doi":"10.1007/978-981-95-0066-6_16","DOIUrl":"10.1007/978-981-95-0066-6_16","url":null,"abstract":"Alzheimer's disease (AD) is a common form of dementia characterized by cognitive decline and abnormal accumulation of proximate neurotoxins in older adults. It accounts for up to 80% of all dementia cases. AD is not exclusively attributed to aging; rather, it involves complex and multifactorial brain changes that can lead to severe functional dependence and ultimately death. Although there has been progress in the development of novel treatments for AD, they are yet to yield disease-modifying effects. Early detection and therapeutic interventions are critical for preventing or delaying the onset of AD. We aimed to provide an overview of emerging evidence on physical exercise as a therapeutic strategy for the prevention and treatment of AD. Studies have demonstrated the potential of exercise in improving cognitive function, reducing the risk of AD, and slowing disease progression by promoting various neuroplastic changes. Therefore, regular exercise should be considered as a disease-modifying intervention for AD and included in comprehensive treatment protocols. Further studies are warranted to establish the optimal exercise regimen for individuals with AD; nonetheless, incorporating exercise into daily routines may contribute toward the prevention and management of AD.","PeriodicalId":7360,"journal":{"name":"Advances in neurobiology","volume":"44 ","pages":"297-316"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Dual Role of Lactate in the Exercising Brain: Fueling Energy and Signaling Fatigue. 乳酸在运动大脑中的双重作用：补充能量和发出疲劳信号。

Advances in neurobiology Pub Date : 2025-01-01 DOI: 10.1007/978-981-95-0066-6_11

Takashi Matsui, Hideaki Soya

{"title":"The Dual Role of Lactate in the Exercising Brain: Fueling Energy and Signaling Fatigue.","authors":"Takashi Matsui, Hideaki Soya","doi":"10.1007/978-981-95-0066-6_11","DOIUrl":"10.1007/978-981-95-0066-6_11","url":null,"abstract":"Historically regarded as a \"fatigue substance\" that impedes muscle contraction, lactate has undergone a paradigm shift in its scientific perception. Currently, it is acknowledged as an indispensable substrate for aerobic ATP synthesis, functioning as a pivotal intermediate in the glycolysis pathway. Within the brain context, lactate derived from glycogen in astrocytes is instrumental in augmenting exercise endurance and enhancing memory formation via the astrocyte-neuron lactate shuttle. This glia-neuron interaction mechanism underscores the expansive influence of lactate beyond mere muscular physiology. Contemporary investigations have pivoted toward elucidating a novel hypothesis: the role of lactate as a ligand for the G protein-coupled receptor (GPR) 81, posited to orchestrate a \"fatigue signal\" amid exercise capabilities. This hypothesized function in neural inhibition underscores the comprehensive impact of lactate on physiological responses to prolonged exercise. This evolving perspective of lactate not only accentuates its central role in metabolic processes but also paves the way for advanced exploration into the whole-body's sophisticated mechanisms for managing and adapting to physical exhaustion and central fatigue.","PeriodicalId":7360,"journal":{"name":"Advances in neurobiology","volume":"44 ","pages":"207-216"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel Ways of Targeting the Dopamine Transporter. 靶向多巴胺转运体的新方法。

Advances in neurobiology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-96364-3_11

Yibin Xu, Hanming Zeng, Shaili Aggarwal, Ole Valente Mortensen

{"title":"Novel Ways of Targeting the Dopamine Transporter.","authors":"Yibin Xu, Hanming Zeng, Shaili Aggarwal, Ole Valente Mortensen","doi":"10.1007/978-3-031-96364-3_11","DOIUrl":"https://doi.org/10.1007/978-3-031-96364-3_11","url":null,"abstract":"Dopamine (DA) is an important modulatory neurotransmitter that is involved in daily activities such as movement, memory, and reward-oriented learning of essential behaviors and needs. DA signaling is initiated by the release of DA into the synaptic cleft that will bind to dopamine receptors to mediate the physiological response. To terminate the DA response, the DA is taken up by the dopamine transporter (DAT), a surface membrane protein. Psychostimulants, like cocaine and amphetamine, both target DAT and interfere with the DA uptake process, resulting in an increased amount of DA in the synaptic cleft. Continuous use of psychostimulants can lead to psychostimulant use disorders (PUDs), which are marked by uncontrollable psychostimulant craving and misuse. Because of the unmet need for treatment options for PUDs, novel strategies for discovering therapies are essential. Over the years, DAT-targeting ligands have been identified with atypical properties such as reduced abuse liability compared to cocaine. These compounds have been proposed to bind to different sites from cocaine and/or prefer and stabilize specific conformations of DAT. In addition, some of these compounds can interfere with psychostimulant-DAT binding and may have therapeutic potential in treating PUDs. This chapter introduces the role of DAT in PUDs, presents the mechanism of action of novel DAT-binding ligands, and discusses the therapeutic potential of atypical DAT-binding ligands for PUDs.","PeriodicalId":7360,"journal":{"name":"Advances in neurobiology","volume":"46 ","pages":"271-292"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0