Clara Ciampi, Francesca Fagiani, Valentina Murtaj, Federica Comella, Veronica Torre, Marta Filibian, Annapaola Andolfo, Clarissa Braccia, Nicola Opallo, Maria Grazia Bottone, Edoardo Pedrini, Elena Lucarini, Maria Bove, Stefano Govoni, Carla Ghelardini, Rosaria Meli, Luigia Trabace, Anna Pittaluga, Giuseppina Mattace Raso, Lorenzo Di Cesare Mannelli, Cristina Lanni
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However, the direct impact of peripheral inflammation on the CNS is largely unknown.</p>\n </section>\n \n <section>\n \n <h3> METHODS</h3>\n \n <p>Using a mouse model of colitis with pain and anxiety-like behavior, we investigated the intricate pathogenic link between colonic inflammation, disruptions in circadian rhythmicity and impaired glymphatic circulation.</p>\n </section>\n \n <section>\n \n <h3> RESULTS</h3>\n \n <p>By in vivo magnetic resonance imaging, we observed a derangement of brain fluid dynamics, with a significant enlargement of the cerebral lateral ventricles and waste deposition within the brain parenchyma. Proteomics revealed changes in cerebrospinal fluid (CSF) composition, enriched in proteins related to inflammation, immune response, complement, neuronal, and lipid metabolic pathways. Alterations in brain metabolite concentrations and in inhibitory control mechanisms and excitatory transmission were detected.</p>\n </section>\n \n <section>\n \n <h3> DISCUSSION</h3>\n \n <p>Colonic inflammation induces remodeling in CSF volume distribution, clearance, and metabolism, with derangement of the crosstalk between neurons and astrocytes, priming synaptopathy.</p>\n </section>\n \n <section>\n \n <h3> HIGHLIGHTS</h3>\n \n <div>\n <ul>\n \n <li>An acute peripheral inflammatory trigger affects the central level by remodeling central nervous system (CNS) fluid distribution and priming early signals of synaptopathy.</li>\n \n <li>A single dextran sulfate sodium (DSS) challenge disrupts the circadian clock machinery and alters CNS fluid distribution, a so far neglected system, thereby impairing glymphatic clearance of waste products and indirectly altering neurotransmitter release dynamics.</li>\n \n <li>These combined effects ultimately impact brain function, extending to the regulation of behavior.</li>\n \n <li>Understanding how an intestinal inflammatory insult may derange the daily rhythm of the mechanisms controlling brain waste disposal may help identify specific groups of subjects at high risk of developing neurological disorders.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1000,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70640","citationCount":"0","resultStr":"{\"title\":\"Intestinal inflammation induces glymphatic remodeling, priming early neurodegenerative signals in male mice\",\"authors\":\"Clara Ciampi, Francesca Fagiani, Valentina Murtaj, Federica Comella, Veronica Torre, Marta Filibian, Annapaola Andolfo, Clarissa Braccia, Nicola Opallo, Maria Grazia Bottone, Edoardo Pedrini, Elena Lucarini, Maria Bove, Stefano Govoni, Carla Ghelardini, Rosaria Meli, Luigia Trabace, Anna Pittaluga, Giuseppina Mattace Raso, Lorenzo Di Cesare Mannelli, Cristina Lanni\",\"doi\":\"10.1002/alz.70640\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> INTRODUCTION</h3>\\n \\n <p>Inflammatory bowel disease triggers extraintestinal manifestations, including in the central nervous system (CNS). However, the direct impact of peripheral inflammation on the CNS is largely unknown.</p>\\n </section>\\n \\n <section>\\n \\n <h3> METHODS</h3>\\n \\n <p>Using a mouse model of colitis with pain and anxiety-like behavior, we investigated the intricate pathogenic link between colonic inflammation, disruptions in circadian rhythmicity and impaired glymphatic circulation.</p>\\n </section>\\n \\n <section>\\n \\n <h3> RESULTS</h3>\\n \\n <p>By in vivo magnetic resonance imaging, we observed a derangement of brain fluid dynamics, with a significant enlargement of the cerebral lateral ventricles and waste deposition within the brain parenchyma. Proteomics revealed changes in cerebrospinal fluid (CSF) composition, enriched in proteins related to inflammation, immune response, complement, neuronal, and lipid metabolic pathways. Alterations in brain metabolite concentrations and in inhibitory control mechanisms and excitatory transmission were detected.</p>\\n </section>\\n \\n <section>\\n \\n <h3> DISCUSSION</h3>\\n \\n <p>Colonic inflammation induces remodeling in CSF volume distribution, clearance, and metabolism, with derangement of the crosstalk between neurons and astrocytes, priming synaptopathy.</p>\\n </section>\\n \\n <section>\\n \\n <h3> HIGHLIGHTS</h3>\\n \\n <div>\\n <ul>\\n \\n <li>An acute peripheral inflammatory trigger affects the central level by remodeling central nervous system (CNS) fluid distribution and priming early signals of synaptopathy.</li>\\n \\n <li>A single dextran sulfate sodium (DSS) challenge disrupts the circadian clock machinery and alters CNS fluid distribution, a so far neglected system, thereby impairing glymphatic clearance of waste products and indirectly altering neurotransmitter release dynamics.</li>\\n \\n <li>These combined effects ultimately impact brain function, extending to the regulation of behavior.</li>\\n \\n <li>Understanding how an intestinal inflammatory insult may derange the daily rhythm of the mechanisms controlling brain waste disposal may help identify specific groups of subjects at high risk of developing neurological disorders.</li>\\n </ul>\\n </div>\\n </section>\\n </div>\",\"PeriodicalId\":7471,\"journal\":{\"name\":\"Alzheimer's & Dementia\",\"volume\":\"21 10\",\"pages\":\"\"},\"PeriodicalIF\":11.1000,\"publicationDate\":\"2025-10-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70640\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Alzheimer's & Dementia\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.70640\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Alzheimer's & Dementia","FirstCategoryId":"3","ListUrlMain":"https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.70640","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Intestinal inflammation induces glymphatic remodeling, priming early neurodegenerative signals in male mice
INTRODUCTION
Inflammatory bowel disease triggers extraintestinal manifestations, including in the central nervous system (CNS). However, the direct impact of peripheral inflammation on the CNS is largely unknown.
METHODS
Using a mouse model of colitis with pain and anxiety-like behavior, we investigated the intricate pathogenic link between colonic inflammation, disruptions in circadian rhythmicity and impaired glymphatic circulation.
RESULTS
By in vivo magnetic resonance imaging, we observed a derangement of brain fluid dynamics, with a significant enlargement of the cerebral lateral ventricles and waste deposition within the brain parenchyma. Proteomics revealed changes in cerebrospinal fluid (CSF) composition, enriched in proteins related to inflammation, immune response, complement, neuronal, and lipid metabolic pathways. Alterations in brain metabolite concentrations and in inhibitory control mechanisms and excitatory transmission were detected.
DISCUSSION
Colonic inflammation induces remodeling in CSF volume distribution, clearance, and metabolism, with derangement of the crosstalk between neurons and astrocytes, priming synaptopathy.
HIGHLIGHTS
An acute peripheral inflammatory trigger affects the central level by remodeling central nervous system (CNS) fluid distribution and priming early signals of synaptopathy.
A single dextran sulfate sodium (DSS) challenge disrupts the circadian clock machinery and alters CNS fluid distribution, a so far neglected system, thereby impairing glymphatic clearance of waste products and indirectly altering neurotransmitter release dynamics.
These combined effects ultimately impact brain function, extending to the regulation of behavior.
Understanding how an intestinal inflammatory insult may derange the daily rhythm of the mechanisms controlling brain waste disposal may help identify specific groups of subjects at high risk of developing neurological disorders.
期刊介绍：
Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.
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