NDLI: Impact of aquaporin-4 and CD11c + microglia in the development of ependymal cells in the aqueduct: inferences to hydrocephalus

Content Provider	Springer Nature : BioMed Central
Author	Mayo, Francisco González-Vinceiro, Lourdes Hiraldo-González, Laura Rodríguez-Gómez, Francisco D. Calle-Castillejo, Claudia Mayo, Manuel Netti, Vanina Ramírez-Lorca, Reposo Echevarría, Miriam
Abstract	AQP4 is expressed in the endfeet membranes of subpial and perivascular astrocytes and in the ependymal cells that line the ventricular system. The sporadic appearance of obstructive congenital hydrocephalus (OCHC) has been observed in the offspring of AQP4−/− mice (KO) due to stenosis of Silvio’s aqueduct. Here, we explore whether the lack of AQP4 expression leads to abnormal development of ependymal cells in the aqueduct of mice. We compared periaqueductal samples from wild-type and KO mice. The microarray-based transcriptome analysis reflected a large number of genes with differential expression (809). Gene sets (GS) associated with ependymal development, ciliary function and the immune system were specially modified qPCR confirmed reduced expression in the KO mice genes: (i) coding for transcription factors for ependymal differentiation (Rfx4 and FoxJ1), (ii) involved in the constitution of the central apparatus of the axoneme (Spag16 and Hydin), (iii) associated with ciliary assembly (Cfap43, Cfap69 and Ccdc170), and (iv) involved in intercellular junction complexes of the ependyma (Cdhr4). By contrast, genes such as Spp1, Gpnmb, Itgax, and Cd68, associated with a Cd11c-positive microglial population, were overexpressed in the KO mice. Electron microscopy and Immunofluorescence of vimentin and γ-tubulin revealed a disorganized ependyma in the KO mice, with changes in the intercellular complex union, unevenly orientated cilia, and variations in the planar cell polarity of the apical membrane. These structural alterations translate into reduced cilia beat frequency, which might alter cerebrospinal fluid movement. The presence of CD11c + microglia cells in the periaqueductal zone of mice during the first postnatal week is a novel finding. In AQP4−/− mice, these cells remain present around the aqueduct for an extended period, showing peak expression at P11. We propose that these cells play an important role in the normal development of the ependyma and that their overexpression in KO mice is crucial to reduce ependyma abnormalities that could otherwise contribute to the development of obstructive hydrocephalus.
Related Links	https://fluidsbarrierscns.biomedcentral.com/counter/pdf/10.1186/s12987-024-00548-2.pdf
Ending Page	23
Page Count	23
Starting Page	1
File Format	HTM / HTML
ISSN	20458118
DOI	10.1186/s12987-024-00548-2
Journal	Fluids and Barriers of the CNS
Issue Number	1
Volume Number	21
Language	English
Publisher	BioMed Central
Publisher Date	2024-07-02
Access Restriction	Open
Subject Keyword	Neurosciences Hematology Neurobiology AQP4−/− Brain Aqueduct Ependyma Cilia Microarray Planar cell polarity CSF CD11c Microglia Electron microscopy Hydrocephalus
Content Type	Text
Resource Type	Article
Subject	Neurology Developmental Neuroscience Medicine Cellular and Molecular Neuroscience
Journal Impact Factor	5.9/2023
5-Year Journal Impact Factor	7.5/2023

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