Physiological reviewsPub Date : 2025-01-01Epub Date: 2024-08-15DOI: 10.1152/physrev.00007.2024
David G Benditt, Artur Fedorowski, Richard Sutton, J Gert van Dijk
{"title":"Pathophysiology of syncope: current concepts and their development.","authors":"David G Benditt, Artur Fedorowski, Richard Sutton, J Gert van Dijk","doi":"10.1152/physrev.00007.2024","DOIUrl":"10.1152/physrev.00007.2024","url":null,"abstract":"<p><p>Syncope is a symptom in which transient loss of consciousness occurs as a consequence of a self-limited, spontaneously terminating period of cerebral hypoperfusion. Many circulatory disturbances (e.g. brady- or tachyarrhythmias, reflex cardioinhibition-vasodepression-hypotension) may trigger a syncope or near-syncope episode, and identifying the cause(s) is often challenging. Some syncope may involve multiple etiologies operating in concert, whereas in other cases multiple syncope events may be due to various differing causes at different times. In this communication, we address the current understanding of the principal contributors to syncope pathophysiology including examination of the manner in which concepts evolved, an overview of factors that constitute consciousness and loss of consciousness, and aspects of neurovascular control and communication that are impacted by cerebral hypoperfusion leading to syncope. Emphasis focuses on <i>1</i>) current understanding of the way transient systemic hypotension impacts brain blood flow and brain function; <i>2</i>) the complexity and temporal sequence of vascular, humoral, and cardiac factors that may accompany the most common causes of syncope; <i>3</i>) the range of circumstances and disease states that may lead to syncope; and <i>4</i>) clinical features associated with syncope and in particular the reflex syncope syndromes.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"209-266"},"PeriodicalIF":29.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Physiological reviewsPub Date : 2025-01-01Epub Date: 2024-03-07DOI: 10.1152/physrev.00014.2023
Dilson E Rassier, Alf Månsson
{"title":"Mechanisms of myosin II force generation: insights from novel experimental techniques and approaches.","authors":"Dilson E Rassier, Alf Månsson","doi":"10.1152/physrev.00014.2023","DOIUrl":"10.1152/physrev.00014.2023","url":null,"abstract":"<p><p>Myosin II is a molecular motor that converts chemical energy derived from ATP hydrolysis into mechanical work. Myosin II isoforms are responsible for muscle contraction and a range of cell functions relying on the development of force and motion. When the motor attaches to actin, ATP is hydrolyzed and inorganic phosphate (P<sub>i</sub>) and ADP are released from its active site. These reactions are coordinated with changes in the structure of myosin, promoting the so-called \"power stroke\" that causes the sliding of actin filaments. The general features of the myosin-actin interactions are well accepted, but there are critical issues that remain poorly understood, mostly due to technological limitations. In recent years, there has been a significant advance in structural, biochemical, and mechanical methods that have advanced the field considerably. New modeling approaches have also allowed researchers to understand actomyosin interactions at different levels of analysis. This paper reviews recent studies looking into the interaction between myosin II and actin filaments, which leads to power stroke and force generation. It reviews studies conducted with single myosin molecules, myosins working in filaments, muscle sarcomeres, myofibrils, and fibers. It also reviews the mathematical models that have been used to understand the mechanics of myosin II in approaches focusing on single molecules to ensembles. Finally, it includes brief sections on translational aspects, how changes in the myosin motor by mutations and/or posttranslational modifications may cause detrimental effects in diseases and aging, among other conditions, and how myosin II has become an emerging drug target.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"1-93"},"PeriodicalIF":29.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140050181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Physiological reviewsPub Date : 2025-01-01Epub Date: 2024-07-25DOI: 10.1152/physrev.00017.2024
Torsten Schöneberg
{"title":"Modulating vertebrate physiology by genomic fine-tuning of GPCR functions.","authors":"Torsten Schöneberg","doi":"10.1152/physrev.00017.2024","DOIUrl":"10.1152/physrev.00017.2024","url":null,"abstract":"<p><p>G protein-coupled receptors (GPCRs) play a crucial role as membrane receptors, facilitating the communication of eukaryotic species with their environment and regulating cellular and organ interactions. Consequently, GPCRs hold immense potential in contributing to adaptation to ecological niches and responding to environmental shifts. Comparative analyses of vertebrate genomes reveal patterns of GPCR gene loss, expansion, and signatures of selection. Integrating these genomic data with insights from functional analyses of gene variants enables the interpretation of genotype-phenotype correlations. This review underscores the involvement of GPCRs in adaptive processes, presenting numerous examples of how alterations in GPCR functionality influence vertebrate physiology or, conversely, how environmental changes impact GPCR functions. The findings demonstrate that modifications in GPCR function contribute to adapting to aquatic, arid, and nocturnal habitats, influencing camouflage strategies, and specializing in particular dietary preferences. Furthermore, the adaptability of GPCR functions provides an effective mechanism in facilitating past, recent, or ongoing adaptations in animal domestication and human evolution and should be considered in therapeutic strategies and drug development.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"383-439"},"PeriodicalIF":29.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141760556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Physiological reviewsPub Date : 2025-01-01Epub Date: 2024-07-11DOI: 10.1152/physrev.00004.2024
Salvatore Incontro, Maria Laura Musella, Malika Sammari, Coralie Di Scala, Jacques Fantini, Dominique Debanne
{"title":"Lipids shape brain function through ion channel and receptor modulations: physiological mechanisms and clinical perspectives.","authors":"Salvatore Incontro, Maria Laura Musella, Malika Sammari, Coralie Di Scala, Jacques Fantini, Dominique Debanne","doi":"10.1152/physrev.00004.2024","DOIUrl":"10.1152/physrev.00004.2024","url":null,"abstract":"<p><p>Lipids represent the most abundant molecular type in the brain, with a fat content of ∼60% of the dry brain weight in humans. Despite this fact, little attention has been paid to circumscribe the dynamic role of lipids in brain function and disease. Membrane lipids such as cholesterol, phosphoinositide, sphingolipids, arachidonic acid, and endocannabinoids finely regulate both synaptic receptors and ion channels that ensure critical neural functions. After a brief introduction on brain lipids and their respective properties, we review here their role in regulating synaptic function and ion channel activity, action potential propagation, neuronal development, and functional plasticity and their contribution in the development of neurological and neuropsychiatric diseases. We also provide possible directions for future research on lipid function in brain plasticity and diseases.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"137-207"},"PeriodicalIF":29.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Physiological reviewsPub Date : 2025-01-01Epub Date: 2024-08-15DOI: 10.1152/physrev.00036.2023
Harris S Kaplan, Patricia M Horvath, Mohammed Mostafizur Rahman, Catherine Dulac
{"title":"The neurobiology of parenting and infant-evoked aggression.","authors":"Harris S Kaplan, Patricia M Horvath, Mohammed Mostafizur Rahman, Catherine Dulac","doi":"10.1152/physrev.00036.2023","DOIUrl":"10.1152/physrev.00036.2023","url":null,"abstract":"<p><p>Parenting behavior comprises a variety of adult-infant and adult-adult interactions across multiple timescales. The state transition from nonparent to parent requires an extensive reorganization of individual priorities and physiology and is facilitated by combinatorial hormone action on specific cell types that are integrated throughout interconnected and brainwide neuronal circuits. In this review, we take a comprehensive approach to integrate historical and current literature on each of these topics across multiple species, with a focus on rodents. New and emerging molecular, circuit-based, and computational technologies have recently been used to address outstanding gaps in our current framework of knowledge on infant-directed behavior. This work is raising fundamental questions about the interplay between instinctive and learned components of parenting and the mutual regulation of affiliative versus agonistic infant-directed behaviors in health and disease. Whenever possible, we point to how these technologies have helped gain novel insights and opened new avenues of research into the neurobiology of parenting. We hope this review will serve as an introduction for those new to the field, a comprehensive resource for those already studying parenting, and a guidepost for designing future studies.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"315-381"},"PeriodicalIF":29.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Physiological reviewsPub Date : 2025-01-01Epub Date: 2024-08-08DOI: 10.1152/physrev.00014.2024
Andreas Nieder
{"title":"The calculating brain.","authors":"Andreas Nieder","doi":"10.1152/physrev.00014.2024","DOIUrl":"10.1152/physrev.00014.2024","url":null,"abstract":"<p><p>The human brain possesses neural networks and mechanisms enabling the representation of numbers, basic arithmetic operations, and mathematical reasoning. Without the ability to represent numerical quantity and perform calculations, our scientifically and technically advanced culture would not exist. However, the origins of numerical abilities are grounded in an intuitive understanding of quantity deeply rooted in biology. Nevertheless, more advanced symbolic arithmetic skills require a cultural background with formal mathematical education. In the past two decades, cognitive neuroscience has seen significant progress in understanding the workings of the calculating brain through various methods and model systems. This review begins by exploring the mental and neuronal representations of nonsymbolic numerical quantity and then progresses to symbolic representations acquired in childhood. During arithmetic operations (addition, subtraction, multiplication, and division), these representations are processed and transformed according to arithmetic rules and principles, leveraging different mental strategies and types of arithmetic knowledge that can be dissociated in the brain. Although it was once believed that number processing and calculation originated from the language faculty, it is now evident that mathematical and linguistic abilities are primarily processed independently in the brain. Understanding how the healthy brain processes numerical information is crucial for gaining insights into debilitating numerical disorders, including acquired conditions like acalculia and learning-related calculation disorders such as developmental dyscalculia.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"267-314"},"PeriodicalIF":29.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Physiological reviewsPub Date : 2025-01-01Epub Date: 2024-08-22DOI: 10.1152/physrev.00011.2024
Svetlana Lutsenko, Shubhrajit Roy, Peter Tsvetkov
{"title":"Mammalian copper homeostasis: physiological roles and molecular mechanisms.","authors":"Svetlana Lutsenko, Shubhrajit Roy, Peter Tsvetkov","doi":"10.1152/physrev.00011.2024","DOIUrl":"10.1152/physrev.00011.2024","url":null,"abstract":"<p><p>In the past decade, evidence for the numerous roles of copper (Cu) in mammalian physiology has grown exponentially. The discoveries of Cu involvement in cell signaling, autophagy, cell motility, differentiation, and regulated cell death (cuproptosis) have markedly extended the list of already known functions of Cu, such as a cofactor of essential metabolic enzymes, a protein structural component, and a regulator of protein trafficking. Novel and unexpected functions of Cu transporting proteins and enzymes have been identified, and new disorders of Cu homeostasis have been described. Significant progress has been made in the mechanistic studies of two classic disorders of Cu metabolism, Menkes disease and Wilson's disease, which paved the way for novel approaches to their treatment. The discovery of cuproptosis and the role of Cu in cell metastatic growth have markedly increased interest in targeting Cu homeostatic pathways to treat cancer. In this review, we summarize the established concepts in the field of mammalian Cu physiology and discuss how new discoveries of the past decade expand and modify these concepts. The roles of Cu in brain metabolism and in cell functional speciation and a recently discovered regulated cell death have attracted significant attention and are highlighted in this review.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":"441-491"},"PeriodicalIF":29.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Motor Control on the Move - from Insights in Insects to General Mechanisms","authors":"Ansgar Büschges, Jan M. Ache","doi":"10.1152/physrev.00009.2024","DOIUrl":"https://doi.org/10.1152/physrev.00009.2024","url":null,"abstract":"Physiological Reviews, Ahead of Print. <br/>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":"201 1","pages":""},"PeriodicalIF":33.6,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142858393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Axon Initial Segment Structure and Function in Health and Disease.","authors":"Paul M Jenkins, Kevin J Bender","doi":"10.1152/physrev.00030.2024","DOIUrl":"10.1152/physrev.00030.2024","url":null,"abstract":"<p><p>At the simplest level, neurons are structured to integrate synaptic input and perform computational transforms on that input, converting it into an action potential (AP) code. This process-converting synaptic input into AP output-typically occurs in a specialized region of axon termed the axon initial segment (AIS). The AIS, as its name implies, is often contained to the first section of axon abutted to the soma and is home to a dizzying array of ion channels, attendant scaffolding proteins, intracellular organelles, extracellular proteins, and, in some cases, synapses. The AIS serves multiple roles as the final arbiter for determining if inputs are sufficient to evoke APs, as a gatekeeper that physically separates the somatodendritic domain from the axon proper, and as a regulator of overall neuronal excitability, dynamically tuning its size to best suit the needs of parent neurons. These complex roles have received considerable attention from experimentalists and theoreticians alike. Here, we review recent advances in our understanding of the AIS and its role in neuronal integration and polarity in health and disease.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":" ","pages":""},"PeriodicalIF":29.9,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}