{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T04:34:22Z","timestamp":1761280462327,"version":"build-2065373602"},"reference-count":55,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spanish Ministry of Economy and Competitiveness, co-financed by the Carlos III Health Institute (ISCIII) and European Regional Development Fund","award":["PI19\/01096"],"award-info":[{"award-number":["PI19\/01096"]}]},{"name":"the Regional Department of Economy, Knowledge, Business and University, Government of An-daluc\u00eda, Andalusian Plan for Research","award":["P20_00646"],"award-info":[{"award-number":["P20_00646"]}]},{"name":"ISCIII, the FORTALECE program of the Spanish Ministry of Science and Innovation","award":["FORT23\/00008"],"award-info":[{"award-number":["FORT23\/00008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Aquaporin-4 (AQP4) is expressed in ependymal cells bordering the ventricles, the glia limitans, and pericapillary astrocyte endfeet forming the blood\u2013brain barrier. The sporadic occurrence of obstructive congenital hydrocephalus (OH) has been observed in the offspring of AQP4\u2212\/\u2212 mice generated in the CD1 strain background. Here, we used microarray analysis to explore gene expression profiles in the periaqueductal area from littermate AQP4\u2212\/\u2212 pups at postnatal day 12. We compared wild-type (WT) animals with AQP4\u2212\/\u2212 animals that developed OH (AQP4\u2212\/\u2212-OH) and those that did not (AQP4\u2212\/\u2212-NH). Bioinformatic analysis identified gene sets associated with proliferation and migration of microglia, ependymal cell adhesion, extracellular matrix components, axon myelination, and neuronal synapsis. Among the differentially expressed genes, Spp1\u2014expressed by neonatal CD11c+ microglia\u2014was highlighted in the triple comparison. Spp1 was significantly upregulated in AQP4\u2212\/\u2212-NH and downregulated in AQP4\u2212\/\u2212-OH mice. These findings suggest that CD11c+ microglia, via Spp1 expression, play a key morphogenic role in the aqueduct of Sylvius and their absence, occurring in a small subset of AQP4\u2212\/\u2212-CD1 animals, leads to obstructive hydrocephalus.<\/jats:p>","DOI":"10.3390\/ijms262110290","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T01:14:02Z","timestamp":1761182042000},"page":"10290","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spp1 Appears to Be a Key Gene for Sporadic Obstructive Hydrocephalus in the Absence of AQP4"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4758-9428","authenticated-orcid":false,"given":"Miriam","family":"Echevarr\u00eda","sequence":"first","affiliation":[{"name":"Instituto de Biomedicina de Sevilla, IBiS, Hospital Universitario Virgen del Roc\u00edo, CSIC, Universidad de Sevilla, 41013 Sevilla, Spain"},{"name":"Departamento de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica, Facultad de Medicina, Universidad de Sevilla, 41009 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Hiraldo-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla, IBiS, Hospital Universitario Virgen del Roc\u00edo, CSIC, Universidad de Sevilla, 41013 Sevilla, Spain"},{"name":"Departamento de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica, Facultad de Medicina, Universidad de Sevilla, 41009 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Luis","family":"Trillo-Contreras","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla, IBiS, Hospital Universitario Virgen del Roc\u00edo, CSIC, Universidad de Sevilla, 41013 Sevilla, Spain"},{"name":"Departamento de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica, Facultad de Medicina, Universidad de Sevilla, 41009 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco D.","family":"Rodr\u00edguez-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla, IBiS, Hospital Universitario Virgen del Roc\u00edo, CSIC, Universidad de Sevilla, 41013 Sevilla, Spain"},{"name":"Departamento de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica, Facultad de Medicina, Universidad de Sevilla, 41009 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco","family":"Mayo","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla, IBiS, Hospital Universitario Virgen del Roc\u00edo, CSIC, Universidad de Sevilla, 41013 Sevilla, Spain"},{"name":"Departamento de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica, Facultad de Medicina, Universidad de Sevilla, 41009 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7707-5041","authenticated-orcid":false,"given":"Elaheh","family":"Sobh-Doush","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla, IBiS, Hospital Universitario Virgen del Roc\u00edo, CSIC, Universidad de Sevilla, 41013 Sevilla, Spain"},{"name":"Departamento de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica, Facultad de Medicina, Universidad de Sevilla, 41009 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Ortiz-Salguero","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla, IBiS, Hospital Universitario Virgen del Roc\u00edo, CSIC, Universidad de Sevilla, 41013 Sevilla, Spain"},{"name":"Departamento de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica, Facultad de Medicina, Universidad de Sevilla, 41009 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2131-9013","authenticated-orcid":false,"given":"Javier","family":"Villadiego","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla, IBiS, Hospital Universitario Virgen del Roc\u00edo, CSIC, Universidad de Sevilla, 41013 Sevilla, Spain"},{"name":"Departamento de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica, Facultad de Medicina, Universidad de Sevilla, 41009 Sevilla, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1594-0404","authenticated-orcid":false,"given":"Reposo","family":"Ram\u00edrez-Lorca","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla, IBiS, Hospital Universitario Virgen del Roc\u00edo, CSIC, Universidad de Sevilla, 41013 Sevilla, Spain"},{"name":"Departamento de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica, Facultad de Medicina, Universidad de Sevilla, 41009 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Del Bigio, M.R. (2024). History of Research Concerning the Ependyma: A View from inside the Human Brain. Front. Cell. Neurosci., 17.","DOI":"10.3389\/fncel.2023.1320369"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1743-8454-5-10","article-title":"Multiplicity of Cerebrospinal Fluid Functions: New Challenges in Health and Disease","volume":"5","author":"Johanson","year":"2008","journal-title":"Cerebrospinal Fluid. Res."},{"key":"ref_3","first-page":"21","article-title":"The Cerebrospinal Fluid and Barriers\u2013Anatomic and Physiologic Considerations","volume":"Volume 146","author":"Tumani","year":"2017","journal-title":"Handbook of Clinical Neurology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"23S","DOI":"10.1097\/00005373-199705001-00005","article-title":"Physiologic Principles for Volume Regulation of a Tissue Enclosed in a Rigid Shell with Application to the Injured Brain","volume":"42","author":"Asgeirsson","year":"1997","journal-title":"J. Trauma-Inj. Infect. Crit. Care"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1007\/s00381-011-1558-y","article-title":"A Consensus on the Classification of Hydrocephalus: Its Utility in the Assessment of Abnormalities of Cerebrospinal Fluid Dynamics","volume":"27","author":"Rekate","year":"2011","journal-title":"Child\u2019s Nerv. Syst."},{"key":"ref_6","first-page":"54","article-title":"Congenital Hydrocephalus: A Review of Recent Advances in Genetic Etiology and Molecular Mechanisms","volume":"11","author":"Liu","year":"2024","journal-title":"Mil. Med. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/B978-0-12-802395-2.00005-5","article-title":"Cerebrospinal Fluid Circulation and Hydrocephalus","volume":"Volume 145","author":"Leinonen","year":"2018","journal-title":"Handbook of Clinical Neurology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1073\/pnas.0437946100","article-title":"An-Syntrophin-Dependent Pool of AQP4 in Astroglial End-Feet Confers Bidirectional Water Flow between Blood and Brain","volume":"100","author":"Otsuka","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.neuint.2010.03.022","article-title":"Regulation of Brain Aquaporins","volume":"57","author":"Zelenina","year":"2010","journal-title":"Neurochem. Int."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S0306-4522(99)00182-7","article-title":"Detailed Localization of Aquaporin-4 Messenger RNA in the CNS: Preferential Expression in Periventricular Organs","volume":"94","author":"Venero","year":"1999","journal-title":"Neuroscience"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1097\/WNR.0000000000000042","article-title":"Water Influx into Cerebrospinal Fluid Is Primarily Controlled by Aquaporin-4, Not by Aquaporin-1","volume":"25","author":"Igarashi","year":"2014","journal-title":"Neuroreport"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Trillo-Contreras, J., Toledo-Aral, J., Echevarr\u00eda, M., and Villadiego, J. (2019). AQP1 and AQP4 Contribution to Cerebrospinal Fluid Homeostasis. Cells, 8.","DOI":"10.3390\/cells8020197"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Trillo-Contreras, J.L., Ram\u00edrez-Lorca, R., Villadiego, J., and Echevarr\u00eda, M. (2022). Cellular Distribution of Brain Aquaporins and Their Contribution to Cerebrospinal Fluid Homeostasis and Hydrocephalus. Biomolecules, 12.","DOI":"10.3390\/biom12040530"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1152\/physrev.00011.2013","article-title":"Physiological Roles of Aquaporin-4 in Brain","volume":"93","author":"Nagelhus","year":"2013","journal-title":"Physiol. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Tham, D.K.L., Joshi, B., and Moukhles, H. (2016). Aquaporin-4 Cell-Surface Expression and Turnover Are Regulated by Dystroglycan, Dynamin, and the Extracellular Matrix in Astrocytes. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0165439"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/nrn3468","article-title":"Aquaporin Water Channels in the Nervous System","volume":"14","author":"Papadopoulos","year":"2013","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-P\u00e9rez, L.M., L\u00f3pez-de-San-Sebasti\u00e1n, J., de Diego, I., Smith, A., Roales-Buj\u00e1n, R., Jim\u00e9nez, A.J., and Paez-Gonzalez, P. (2024). A Selective Defect in the Glial Wedge as Part of the Neuroepithelium Disruption in Hydrocephalus Development in the Mouse Hyh Model Is Associated with Complete Corpus Callosum Dysgenesis. Front. Cell. Neurosci., 18.","DOI":"10.3389\/fncel.2024.1330412"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/978-3-7091-0923-6_12","article-title":"Hydrocephalus and Aquaporins: The Role of Aquaporin-4","volume":"113","author":"Filippidis","year":"2012","journal-title":"Acta Neurochir. Suppl."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/978-3-7091-0923-6_11","article-title":"Hydrocephalus and Aquaporins: The Role of Aquaporin-1","volume":"113","author":"Kalani","year":"2012","journal-title":"Acta Neurochir. Suppl."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1002\/ana.25046","article-title":"Deconstructing Normal Pressure Hydrocephalus: Ventriculomegaly as Early Sign of Neurodegeneration","volume":"82","author":"Espay","year":"2017","journal-title":"Ann. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1096\/fj.04-1711fje","article-title":"Reduced Cerebrospinal Fluid Production and Intracranial Pressure in Mice Lacking Choroid Plexus Water Channel Aquaporin-1","volume":"19","author":"Oshio","year":"2005","journal-title":"FASEB J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1111\/j.1365-2990.2012.01275.x","article-title":"Differences in Distribution and Regulation of Astrocytic Aquaporin-4 in Human and Rat Hydrocephalic Brain","volume":"39","author":"Skjolding","year":"2013","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.neuroimage.2009.04.070","article-title":"Aquaporin 4 Correlates with Apparent Diffusion Coefficient and Hydrocephalus Severity in the Rat Brain: A Combined MRI\u2013Histological Study","volume":"47","author":"Tourdias","year":"2009","journal-title":"Neuroimage"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1002\/jnr.21927","article-title":"Sporadic Obstructive Hydrocephalus in Aqp4 Null Mice","volume":"87","author":"Feng","year":"2009","journal-title":"J. Neurosci. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.neuroscience.2009.04.044","article-title":"Aquaporin-4 Maintains Ependymal Integrity in Adult Mice","volume":"162","author":"Li","year":"2009","journal-title":"Neurosciences"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s12987-024-00548-2","article-title":"Impact of Aquaporin-4 and CD11c+ Microglia in the Development of Ependymal Cells in the Aqueduct: Inferences to Hydrocephalus","volume":"21","author":"Mayo","year":"2024","journal-title":"Fluids Barriers CNS"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Mayo, F., Gonz\u00e1lez-Vinceiro, L., Hiraldo-Gonz\u00e1lez, L., Calle-Castillejo, C., Torres-Rubio, I., Mayo, M., Ram\u00edrez-Lorca, R., and Echevarr\u00eda, M. (2024). Absence of Aquaporin-4 (AQP4) Prolongs the Presence of a CD11c+ Microglial Population during Postnatal Corpus Callosum Development. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25158332"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1016\/j.cell.2018.05.003","article-title":"Disease-Associated Microglia: A Universal Immune Sensor of Neurodegeneration","volume":"173","author":"Deczkowska","year":"2018","journal-title":"Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e101997","DOI":"10.15252\/embj.2019101997","article-title":"Microglial Subtypes: Diversity within the Microglial Community","volume":"38","author":"Stratoulias","year":"2019","journal-title":"EMBO J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.neuron.2018.12.006","article-title":"Developmental Heterogeneity of Microglia and Brain Myeloid Cells Revealed by Deep Single-Cell RNA Sequencing","volume":"101","author":"Li","year":"2019","journal-title":"Neuron"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1038\/s41586-019-0924-x","article-title":"Spatial and Temporal Heterogeneity of Mouse and Human Microglia at Single-Cell Resolution","volume":"568","author":"Masuda","year":"2019","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1016\/j.cell.2024.01.012","article-title":"Microglia Maintain Structural Integrity during Fetal Brain Morphogenesis","volume":"187","author":"Lawrence","year":"2024","journal-title":"Cell"},{"key":"ref_33","unstructured":"Oliveros, J.C. (2025, September 21). Venny. An Interactive Tool for Comparing Lists with Venn\u2019s Diagrams. Available online: https:\/\/bioinfogp.cnb.csic.es\/tools\/venny\/index.html."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Supek, F., Bo\u0161njak, M., \u0160kunca, N., and \u0160muc, T. (2011). Revigo Summarizes and Visualizes Long Lists of Gene Ontology Terms. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0021800"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Eden, E., Navon, R., Steinfeld, I., Lipson, D., and Yakhini, Z. (2009). GOrilla: A Tool for Discovery and Visualization of Enriched GO Terms in Ranked Gene Lists. BMC Bioinform., 10.","DOI":"10.1186\/1471-2105-10-48"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.tox.2018.11.011","article-title":"Strain Differences between CD-1 and C57BL\/6 Mice in Expression of Metabolic Enzymes and DNA Methylation Modifications of the Primary Hepatocytes","volume":"412","author":"Wang","year":"2019","journal-title":"Toxicology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.immuni.2018.11.004","article-title":"Single Cell RNA Sequencing of Microglia throughout the Mouse Lifespan and in the Injured Brain Reveals Complex Cell-State Changes","volume":"50","author":"Hammond","year":"2019","journal-title":"Immunity"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.gde.2020.06.013","article-title":"Microglial Ontogeny, Diversity and Neurodevelopmental Functions","volume":"65","author":"Thion","year":"2020","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1016\/j.cell.2018.06.021","article-title":"Molecular Architecture of the Mouse Nervous System","volume":"174","author":"Zeisel","year":"2018","journal-title":"Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3982","DOI":"10.1074\/jbc.RA119.011541","article-title":"The Complex of Outer-Arm Dynein Light Chain-1 and the Microtubule-Binding Domain of the \u03b3 Heavy Chain Shows How Axonemal Dynein Tunes Ciliary Beating","volume":"295","author":"Toda","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1007\/s12640-023-00646-3","article-title":"Connexin 43 Promotes Neurogenesis via Regulating Aquaporin-4 after Cerebral Ischemia","volume":"41","author":"Chu","year":"2023","journal-title":"Neurotox. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.bbi.2021.08.232","article-title":"The Role of AQP4 in the Pathogenesis of Depression, and Possible Related Mechanisms","volume":"98","author":"Genel","year":"2021","journal-title":"Brain. Behav. Immun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/s41582-025-01081-y","article-title":"Multiple Sclerosis: An Immune Attack on Astrocyte-Mediated Ion and Water Homeostasis","volume":"21","year":"2025","journal-title":"Nat. Rev. Neurol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/s41582-020-00432-1","article-title":"Hypomyelinating Leukodystrophies-Unravelling Myelin Biology","volume":"17","author":"Wolf","year":"2021","journal-title":"Nat. Rev. Neurol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Mayo, F., Gonz\u00e1lez-Vinceiro, L., Hiraldo-Gonz\u00e1lez, L., Calle-Castillejo, C., Morales-Alvarez, S., Ram\u00edrez-Lorca, R., and Echevarr\u00eda, M. (2023). Aquaporin-4 Expression Switches from White to Gray Matter Regions during Postnatal Development of the Central Nervous System. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24033048"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1002\/(SICI)1098-1136(199903)26:1<47::AID-GLIA5>3.0.CO;2-5","article-title":"Immunogold Evidence Suggests That Coupling of K+ Siphoning and Water Transport in Rat Retinal M\u00fcller Cells Is Mediated by a Coenrichment of Kir4.1 and AQP4 in Specific Membrane Domains","volume":"26","author":"Nagelhus","year":"1999","journal-title":"Glia"},{"key":"ref_47","first-page":"20","article-title":"The Postnatal Expression of Transcripts and Proteins in the Corpus Callosum, as Well as Its Myelinization, Is Affected by the Congenital Absence of AQP4","volume":"82","author":"Mayo","year":"2025","journal-title":"J. Physiol. Biochem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbrc.2023.01.039","article-title":"Regulation of the V-ATPase Subunit ATP6V0D2 and Its Role in Demyelination after Peripheral Nerve Injury","volume":"646","author":"Shin","year":"2023","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Chen, S., Wang, H., Zhang, L., Xi, Y., Lu, Y., Yu, K., Zhu, Y., Regina, I., and Bi, Y. (2025). Glymphatic System: A Self-Purification Circulation in Brain. Front. Cell. Neurosci., 19.","DOI":"10.3389\/fncel.2025.1528995"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e82232","DOI":"10.7554\/eLife.82232","article-title":"Loss of Aquaporin-4 Results in Glymphatic System Dysfunction via Brain-wide Interstitial Fluid Stagnation","volume":"12","author":"Gomolka","year":"2023","journal-title":"eLife"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1172\/JCI231","article-title":"Generation and Phenotype of a Transgenic Knockout Mouse Lacking the Mercurial-Insensitive Water Channel Aquaporin-4","volume":"100","author":"Ma","year":"1997","journal-title":"J. Clin. Investig."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene Set Enrichment Analysis: A Knowledge-Based Approach for Interpreting Genome-Wide Expression Profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene Ontology: Tool for the Unification of Biology","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"iyad031","DOI":"10.1093\/genetics\/iyad031","article-title":"The Gene Ontology Knowledgebase in 2023","volume":"224","author":"Aleksander","year":"2023","journal-title":"Genetics"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","article-title":"The Molecular Signatures Database Hallmark Gene Set Collection","volume":"1","author":"Liberzon","year":"2015","journal-title":"Cell Syst."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/21\/10290\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T04:30:31Z","timestamp":1761280231000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/21\/10290"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,22]]},"references-count":55,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["ijms262110290"],"URL":"https:\/\/doi.org\/10.3390\/ijms262110290","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,10,22]]}}}