Deconstructing the functional neuroanatomy of the choroid plexus: an ontogenetic perspective for studying neurodevelopmental and neuropsychiatric disorders

Abstract

The choroid plexus (CP) is a delicate and highly vascularized structure in the brain comprised of a dense network of fenestrated capillary loops that help in the synthesis, secretion and circulation of cerebrospinal fluid (CSF). This unique neuroanatomical structure is comprised of arachnoid villi stemming from frond-like surface projections—that protrude into the lumen of the four cerebral ventricles—providing a key source of nutrients to the brain parenchyma in addition to serving as a ‘sink’ for central nervous system metabolic waste. In fact, the functions of the CP are often described as being analogous to those of the liver and kidney. Beyond forming a barrier/interface between the blood and CSF compartments, the CP has been identified as a modulator of leukocyte trafficking, inflammation, cognition, circadian rhythm and the gut brain-axis. In recent years, advances in molecular biology techniques and neuroimaging along with the use of sophisticated animal models have played an integral role in shaping our understanding of how the CP–CSF system changes in relation to the maturation of neural circuits during critical periods of brain development. In this article we provide an ontogenetic perspective of the CP and review the experimental evidence implicating this structure in the pathophysiology of neurodevelopmental and neuropsychiatric disorders.

Choroid Plexus Enlargement Exacerbates White Matter Hyperintensity Growth through Glymphatic Impairment

“…Its single-layer epithelial basement membrane surrounds a delicate network of fenestrated capillaries and connective tissue composed of fibroblasts and immune cells. 3 Producing cerebrospinal fluid (CSF), forming the blood-CSF barrier and responsible for peripheral-central immune surveillance, [3][4][5] CP is among the least studied structures of the central nervous system despite its clinical importance. CP enlargement has been widely reported in patients with neurodegenerative 6 and neuroinflammatory diseases, 7 but few studies have focused on its involvement in WMH, which is promoted by inflammation and is a common precursor of dementia.…”

Eye movement defects in KO zebrafish reveals SRPK3 as a causative gene for an X-linked intellectual disability

“…The choroid plexus (CP) is a highly vascularized structure in the brain which helps with synthesis, secretion, and circulation of CSF. The structural and functional implications of the CP in brain diseases have been neglected for many years; however, in recent years the CP has gained attention as a neuroanatomical structure directly linked to neurodevelopmental and neuropsychiatric disorders [50]. Since SRPK3 is highly expressed in the CP epithelium, it will be…”

Faulty fences: Blood-brain barrier dysfunction in schizophrenia

“…In addition to the issues described regarding the BBB, the blood-CSF barrier at the choroid plexus may also be insufficient in schizophrenia (Box, [27][28][29][30][31] page 31).…”

“…30 Less claudin-5 at the choroid plexus in schizophrenia implicates similar permissive effects as seen at the BBB. 31 Although the contribution of blood-CSF barrier dysfunction to schizophrenia requires further study, reduced barrier function outside the BBB is a viable line of inquiry.…”