[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-465229-105":59,"doc-detail-465229-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","brain-synapses-neurons-astrocytes-and-extracellular-vesicles-in-health-and-diseases","Brain Synapses: Neurons, Astrocytes, and Extracellular Vesicles in Health and Diseases","","Synapses in the brain are essential life structures, shaped by evolving concepts of health and disease. Cell-to-cell axon communication, guidance, and synapse orientation drive growth and organization of pre- and post-synaptic terminals through liquid–liquid phase behavior regulated by Ca2+ responses in astrocyte domains. During stimulation, synaptic clefts expand while thickness remains stable. Neurons cooperate with astrocytes and extracellular vesicles (EVs), where diverse responses modulate synaptic signaling. Pre-synaptic behavior is classified as canonical when neurotransmitter release is involved, or non-canonical when EV-driven mechanisms act without neurotransmitter release. Health and neurodegenerative disease outcomes depend on molecular properties, including Alzheimer’s-related features, astrocyte/microglia contributions, and EV-induced effects. Therapeutic complexity is increasing, with emerging initiatives despite limited current success.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/brain-synapses-neurons-astrocytes-and-extracellular-vesicles-in-health-and-diseases/465229/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/brain-synapses-neurons-astrocytes-and-extracellular-vesicles-in-health-and-diseases/465229.png","ImageObject",300,407,{"name":92,"@type":93},"Valentina","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What structural changes occur during synapse stimulation?","Question",{"text":112,"@type":113},"Upon stimulation, synaptic clefts expand several folds, while the thickness of pre- and post-synaptic regions remains unchanged.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How are pre-synaptic responses classified in this review?",{"text":117,"@type":113},"Responses are canonical when based on neurotransmitter release, and non-canonical when they occur without release and are mediated by extracellular vesicles (EVs).",{"name":119,"@type":110,"acceptedAnswer":120},"Which cell types and mechanisms are emphasized for health and disease relevance?",{"text":121,"@type":113},"Astrocytes and microglia, along with EV secretions and molecularly defined properties, are highlighted as critical contributors to health and neurodegenerative disease outcomes, including Alzheimer’s-related features.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},465229,1790902250,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":41,"preview_page_count":4},13056703020460,"https://ap-avatar.wpscdn.com/avatar/be000253dac470eee5d?_k=1778207105932848923","Review  \nBrain Synapses: Neurons, Astrocytes, and Extracellular Vesicles in Health and Diseases  \nJacopo Meldolesi 1,2  \nAcademic Editors: Sung-Kun (Sean) Kim and Kwang Choi  \nReceived: 24 September 2025  \nRevised: 9 December 2025  \nAccepted: 11 December 2025  \nPublished: 23 December 2025  \nCopyright: © 2025 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.  \n1 IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20129 Milan, Italy; meldolesi.jacopo@hsr.it  \n2 CNR Institute of Neuroscience, Milano-Bicocca University, 20854 Milan, Italy  \nAbstract  \nSynapses, abundant in the brain, are structures needed for life. Our Introduction, based on the forms of such structures published few decades ago, helped in developing recent concepts of health and diseases. Growing axons govern their growth by cell-to-cell communication, axon guidance, and synapse orientations. The assembly of synapses requires the organization and function of pre-synaptic and post-synaptic neuronal terminals with a liquid–liquid phase, governed by Ca2+ responses of thin astrocyte domains. Upon synapse stimulation, the clefts expand up to several folds while pre-and post-synaptic thickness remains unchanged. In additional responses, neurons co-operate with astrocytes and extracellular vesicles (EVs), the latter dependent on extracellular and intracellular spaces. Astrocyte and microglia cells and/or EV secretions induce neurons by various effects including traveling changes. Pre-synaptic responses are defined as canonical if based on neurotransmitter release; non-canonical if they are without release and are discharged by EVs, not neurotransmitters. Health and diseases depend on other general properties, such as those defined molecularly. Among neurodegenerative diseases, attention is specified by various properties of Alzheimer’s and other diagnoses. Critical identifications can be due to astrocyte and microglia cells or multiple effects induced by EVs. At present, the complexity of therapies, although of limited success, is developing innovative initiatives.  \nKeywords: Alzheimer’s; amyloid-β; Arc; astrocyte; axon; biomarket; canonical; cell-to-cell; clathrin; cleft; clinical/therapeutic; dendrite; endocytic; exocytosis; glia; microglia; navigation; neurotransmitter; polyphenolic; pre-synaptic/post-synaptic; reclustered; recycling; special issue; spine; synaptic vesicle; strokes; SubType; tau; trails/impact; triplets  \n1. Introduction  \nThe present Special Issue (SI) deals with synapses existing in the central nervous system (CNS), which have been known for a long time but only recognized by innovated properties identified during the last several years. Considering the developments that take place during the Introduction, I note that at least half of the presented information is due to well-known published events before 2018 . A fraction of additional information, published more recently, has been recognized and related directly or connected to previously reported events. Because of the nature of their coordination, the properties presented in this Introduction anticipate recent mechanisms and processes presented in the following sections of this review.  \nThe first step presented here includes the appearance of axons, the first components of synapses including the somato-dendritic compartments of neurons. Such axons are distinct in various properties: composition, diameter, and length [1] . The formation of axons  \nincludes progressive extension accompanied by navigation and orientation. Axonal length varies among synapses. Altogether, however, the axons account for high fractions of whole neuronal volumes [2] . In most neurons, the axon is initially single, then organized into multiple branches. Its activity depends mostly on voltage-gated ion channels, necessary for the activity of their action potentials. Membran","cbCaituLTfG9uIhr","https://ap.wps.com/l/cbCaituLTfG9uIhr","pdf",848340,12,"English","# Abstract\n# Keywords\n# 1. Introduction\n## Axon formation and organization\n## Pre-synaptic and post-synaptic coordination\n## Dendrite signaling and receptor regulation","[{\"question\":\"What structural changes occur during synapse stimulation?\",\"answer\":\"Upon stimulation, synaptic clefts expand several folds, while the thickness of pre- and post-synaptic regions remains unchanged.\"},{\"question\":\"How are pre-synaptic responses classified in this review?\",\"answer\":\"Responses are canonical when based on neurotransmitter release, and non-canonical when they occur without release and are mediated by extracellular vesicles (EVs).\"},{\"question\":\"Which cell types and mechanisms are emphasized for health and disease relevance?\",\"answer\":\"Astrocytes and microglia, along with EV secretions and molecularly defined properties, are highlighted as critical contributors to health and neurodegenerative disease outcomes, including Alzheimer’s-related features.\"}]","Brain Synapses: Neurons, Astrocytes, and Extracellular Vesicles in Health and Diseases | PDF",1790769346]