Experimental approaches for manipulating choroid plexus epithelial cells

• Published in: Fluids and barriers of the CNS Vol. 19; no. 1; p. 36
• Main Authors: Jang, Ahram, Lehtinen, Maria K
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 26-05-2022; BioMed Central; BMC
• Subjects: Adeno-associated virus (AAV); Amyloid beta-Peptides; Artificial chromosomes; Blood-cerebrospinal fluid barrier (BCSFB); Cell Count; Central nervous system; Cerebrospinal fluid; Cerebrospinal fluid (CSF); Chemogenetics; Choroid Plexus; Choroid plexus (ChP); Circadian rhythm; Cogeneration power plants; Drug therapy; Epithelial Cells; Epithelium; Gene expression; Gene therapy; Gene transfer; Genes; Genetic engineering; Mammals; Nervous system diseases; Neurodevelopmental disorders; Neurological diseases; Review; Rodents; Transgenic animals; Transplantation; Adeno-associated virus (AAV); Choroid plexus (ChP); Blood-cerebrospinal fluid barrier (BCSFB); Cerebrospinal fluid (CSF); Gene therapy; Chemogenetics
• ISSN: 2045-8118; 2045-8118
• DOI: 10.1186/s12987-022-00330-2

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.