5 - Physiological Roles of Aquaporins in the Choroid Plexus
Section snippets
Aquaporin Water Channels
Aquaporins (AQPs) are members of the Major Intrinsic Protein (MIP) family. To date, eleven members, designated AQP0 through 10, have been characterized in mammals, and more than 150 related members of the MIP family are found in plants, bacteria, invertebrates, and nonmammalian vertebrates (reviewed by Amiry-Moghaddam and Ottersen, 2003). In choroid plexus, the contribution of aquaporin water channels is essential, considering that this tissue serves as the dominant route for water entry into
Development of the Choroid Plexus
Choroid plexus develops on the dorsal side of the neural tube following its closure. It originates from neuroepithelium, and appears between the sixth and eighth weeks of gestation in humans (Netsky and Shuangshoti, 1975a, Netsky and Shuangshoti, 1975b), initially in the roof of the fourth ventricle, then in the lateral ventricles, and finally in the third ventricle. By 9 weeks gestation, the fetal choroid plexus is proportionately larger than in the adult (relative to total brain size), and
Ion Channels in the Choroid Plexus
The choroid plexus epithelial cells are characteristically polarized: the apical membrane faces the lumen of the ventricles and the basolateral membrane faces the blood side where the capillaries are present (Fig. 2a). Numerous classes of ion channels and transporters are targeted specifically to each side of the cellular membrane, and they all work in concert to secrete CSF. The first step in this process is the filtration of plasma at the level of the choroidal capillary endothelium; the
Function of AQP1 as a Gated Cation Channel
Data from studies of AQP1 suggest that it may also contribute as a gated ion channel, as well as a water channel, to the function of choroid plexus. Aquaporins are known for mediating transport of water and glycerol, but additional roles as regulated ion channels have become evident. Thus far, several members of the aquaporin family have been described as both water channels and ion channels: AQP0, AQP1, and AQP6 (Anthony et al., 2000, Ehring et al., 1990, Ehring et al., 1992, Hazama et al.,
Physiological Relevance of AQP1 Ion Channels in Choroid Plexus
In primary cultures of rat choroid plexus, native AQP1 mediates a robust cyclic-GMP-gated conductance with channel properties similar to those described previously in the oocyte expression system (Boassa, Stamer, and Yool, unpublished data). Activation and block of the AQP1-mediated ionic current altered net fluid movement across the choroid plexus barrier in vitro, suggesting that the AQP1-mediated ionic conductance has physiological significance for the regulation of cerebrospinal fluid
Regulation of Cerebrospinal Fluid Production
Several signaling cascades in addition to that regulated by ANP have a direct effect on transporters and ion channels present in the choroid plexus epithelium, altering their transport activity and therefore modulating the net transcellular movement of solutes and water. Receptors for serotonin (5-HT), arginine vasopressin (AVP), and norepinephrine have been localized to the choroid plexus epithelium (for review, see (Nilsson et al., 1992b). The receptor for serotonin (5-HT1C) is highly
Choroid Plexus “Dark Cells”
An interesting morphological correlate of the functional state of choroid plexus cells has been inferred from the presence of “dark cells.” Wislocki and Ladman (1958) were the first to describe two different cell types in the choroid plexus epithelium, called “light” and “dark” epithelial cells, based on their anatomical appearance at the microscopic level. The authors suggested that the difference in apparent cytoplasmic density between the two cell types could reflect different phases in the
Barrier Function of the Choroid Plexus
Comparing the compositions of CSF and plasma (Table I), it is important to note in the CSF the lower levels of proteins and amino acids and the slightly lower pH. CSF ion homeostasis is vital and the choroid plexus is responsible for keeping a stable composition of solutes, buffering the system against the wide changes that can occur in blood plasma. For example, it is essential to maintain comparatively lower levels of K+ and Ca2 + in CSF, since even small changes in their concentration can
Neuroendocrine Function
The choroid plexus acts as both a target and a source for hormonal and neuroendocrine signals within the brain. The circulating CSF produced by choroid plexus conveys the signaling molecules that are selectively imported or generated by choroid plexus, such as hormones and growth factors, throughout the brain. Hormones moving from the blood to the CSF through the choroid plexus epithelium can reach their target area in the brain by diffusing through the brain interstitial fluid. Neuroendocrine
Pathophysiology of the Choroid Plexus
The net movement of water across the blood–brain and the blood–CSF barriers is important in the regulation of brain water content. Water imbalance in the brain can have serious and life-threatening implications, such as altered excitability and neurodegeneration, disruption of the supply of nutrients, loss of signaling molecules, and the accumulation of unwanted toxins and metabolites. Hydrocephalus is a hydrodynamic disorder that consists of an increase in CSF volume within the cranial cavity,
Conclusions
Understanding the mechanisms involved in the modulation of CSF secretion is of fundamental importance. An appreciation of AQP1 as an ion channel in addition to its role as a water channel should offer new targets for therapeutic strategies in diseases involving water imbalance in the brain. AQP1 is highly expressed in the choroid plexus, and understanding its functional properties might reveal it as a potential target for regulating water and salt movements in development, homeostasis, and
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Aquaporin-4 in glymphatic system, and its implication for central nervous system disorders
2023, Neurobiology of DiseaseExploring the role of astrocytic dysfunction and AQP4 in depression
2022, Cellular SignallingCitation Excerpt :In the CNS, AQP1, AQP4, and AQP9 were expressed [20]. AQP1 is present primarily in the choroid plexus and is implicated in the secretion of CSF [43,44]. AQP9 is expressed primarily in the periventricular areas and is involved in energy homeostasis [45,46].
Characterization of the circadian oscillator in the choroid plexus of rats
2020, Biochemical and Biophysical Research CommunicationsCitation Excerpt :Indeed, CSF secretion shows diurnal variation with a nightly peak in humans [31,32]. APQ1 plays an important role in CSF secretion, and is located on the apical side of epithelial cells of CP [10,33,34]. In this study, dusk-to-dawn variation of AQP1 expression was not found.
Structure, function and translational relevance of aquaporin dual water and ion channels
2012, Molecular Aspects of MedicineCitation Excerpt :AQP1 is expressed in barrier epithelia at which the maintenance of fluid homeostatic balance is essential, and their roles in facilitating water flux in these tissues is evident. In choroid plexus in brain ventricles, AQP1 enables the production of cerebral spinal fluid (Boassa and Yool, 2005; Johansson et al., 2005). In kidney proximal tubule and descending thin limb of Henley, AQP1 enables efficient fluid reabsorption (Ma et al., 1998).
microRNA-449 is a putative regulator of choroid plexus development and function
2009, Brain ResearchCitation Excerpt :In addition, Aquaporin-1, a water channel, also plays an important role in maintaining the equilibrium in volume and composition of the CSF (Oshio et al. 2005). These channels are affected by different signalling cascades altering their transport activity and therefore adjusting the movement of solutes and water (Boassa and Yool 2005). One of these pathways is regulated by transcription factor E2f5, which is specifically expressed in CPs (Swetloff and Ferretti 2005).