Aberrant adenosine A_2A receptor signaling in the choroid plexus drives CSF hypersecretion and ventriculomegaly in hydrocephalus.

ABSTRACT: Hydrocephalus is a common and serious neuropathological condition characterized by disrupted cerebrospinal fluid (CSF) circulation, which lacks effective pharmacotherapy. Here, we demonstrate that adenosine A_2A receptor (A_2AR) signaling in the choroid plexus (ChP) is a trigger of hydrocephalus. Adenosine levels are increased in the CSF of hydrocephalus patients and mice, together with elevated ChP-A_2AR density. Accordingly, continued infusion of adenosine for 14 days or transgenic ChP-A_2AR overexpression is sufficient to drive CSF hypersecretion and ventriculomegaly. Conversely, selective knockdown of ChP-A_2AR reduces CSF production and ameliorates CSF hypersecretion and ventriculomegaly induced by autologous blood and kaolin. Furtherm

SUBMITTER: Zheng W 

PROVIDER: S-EPMC12770498 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature