Kidins220-deficient hydrocephalus mice exhibit altered glial phenotypes and AQP4 differential regulation in the retina and optic nerve, with preserved retinal ganglion cell survival.

ABSTRACT: Hydrocephalus, characterized by ventriculomegaly due to cerebrospinal fluid accumulation in the cerebral ventricles, is a co-morbidity factor in several neurodevelopmental, psychiatric and neurodegenerative diseases. Aquaporin-4 (AQP4) is crucial for brain water homeostasis, with Aqp4 knockout mice showing sporadic ventriculomegaly and increased brain water content. Kinase D interacting substrate of 220 kDa (Kidins220), a transmembrane protein involved in neuronal survival, synaptic activity and neurogenesis, controls AQP4 levels in ependymocytes and brain astrocytes. Indeed, Kidins220 deficiency in mice leads to hydrocephalus by downregulating VPS35, a key component of the retromer complex, and targeting AQP4 to lysosomal degradation. Importantly, the ependymal barrier of idiopathic norma

SUBMITTER: Fernandez-Albarral JA 

PROVIDER: S-EPMC11823095 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature