Experimental approaches for manipulating choroid plexus epithelial cells

Abstract

Choroid plexus (ChP) epithelial cells are crucial for the function of the blood-cerebrospinal fluid barrier (BCSFB) in the developing and mature brain. The ChP is considered the primary source and regulator of CSF, secreting many important factors that nourish the brain. It also performs CSF clearance functions including removing Amyloid beta and potassium. As such, the ChP is a promising target for gene and drug therapy for neurodevelopmental and neurological disorders in the central nervous system (CNS). This review describes the current successful and emerging experimental approaches for targeting ChP epithelial cells. We highlight methodological strategies to specifically target these cells for gain or loss of function in vivo. We cover both genetic models and viral gene delivery systems. Additionally, several lines of reporters to access the ChP epithelia are reviewed. Finally, we discuss exciting new approaches, such as chemical activation and transplantation of engineered ChP epithelial cells. We elaborate on fundamental functions of the ChP in secretion and clearance and outline experimental approaches paving the way to clinical applications.

In utero intracerebroventricular delivery of adeno-associated viral vectors to target mouse choroid plexus and cerebrospinal fluid

“…We transduced AAVs, particularly the AAV2/5 serotype, due to its tropism for the choroid plexus (ChP) at this age. 1 , 2 The protocol below shows an example using CD1 mice that have large litters. However, we have also used this protocol with C57BL/6 mice or transgenic/knockout mice with C57BL/6J backgrounds.…”

“…We used AAV5 for targeting ChP from embryonic stage E13.5 injection. AAV9 has also been shown to target ChP after E15 injection and to persist for months, while other serotypes have not shown ChP specificity (Table 2 in Jang and Lehtinen 2 ).…”

A year in review: brain barriers and brain fluids research in 2022

“…Understanding the roles of the choroid plexus would be greatly assisted by developing methods to specifically target choroid plexus epithelial cells to induce loss or gain of function. Jang & Lehtinen [ 62 ] have recently reviewed progress in that area. It would also be assisted by developing new in vitro choroid plexus epithelium models.…”

Choroid plexus epithelium and its role in neurological diseases

“…For the methods of virus administration in gene therapy, some articles have reviewed this (Jang and Lehtinen, 2022), and several methods of intravenous administration such as ultrasound-guided intrauterine vena cava administration have been proposed. The hazards of adenovirus use are also described in this article.…”