Neuroimmunological Implications of AQP4 in Astrocytes

Abstract

The brain has high-order functions and is composed of several kinds of cells, such as neurons and glial cells. It is becoming clear that many kinds of neurodegenerative diseases are more-or-less influenced by astrocytes, which are a type of glial cell. Aquaporin-4 (AQP4), a membrane-bound protein that regulates water permeability is a member of the aquaporin family of water channel proteins that is expressed in the endfeet of astrocytes in the central nervous system (CNS). Recently, AQP4 has been shown to function, not only as a water channel protein, but also as an adhesion molecule that is involved in cell migration and neuroexcitation, synaptic plasticity, and learning/memory through mechanisms involved in long-term potentiation or long-term depression. The most extensively examined role of AQP4 is its ability to act as a neuroimmunological inducer. Previously, we showed that AQP4 plays an important role in neuroimmunological functions in injured mouse brain in concert with the proinflammatory inducer osteopontin (OPN). The aim of this review is to summarize the functional implication of AQP4, focusing especially on its neuroimmunological roles. This review is a good opportunity to compile recent knowledge and could contribute to the therapeutic treatment of autoimmune diseases through strategies targeting AQP4. Finally, the author would like to hypothesize on AQP4’s role in interaction between reactive astrocytes and reactive microglial cells, which might occur in neurodegenerative diseases. Furthermore, a therapeutic strategy for AQP4-related neurodegenerative diseases is proposed.

Diffusion MRI reveals in vivo and non-invasively changes in astrocyte function induced by an aquaporin-4 inhibitor

“…Deletion of the AQP4 gene suppresses the clearance of soluble amyloid β [1]. As a consequence of the regulation of astrocyte membrane water permeability, AQP4 is involved in the rapid volume regulation of astrocytes [13]. Although most studies were performed in vitro , some studies showed astrocyte volume change in vivo using 2-photon microscopy.…”

AQP4‑knockout alleviates the lipopolysaccharide‑induced inflammatory response in astrocytes via SPHK1/MAPK/AKT signaling

“…astrocytes, a major component of the neural network, are increasingly being recognized for their importance in neuroimmunity, including responsiveness to il-1 (6), removal of old cells and secretion of tnf-α/il- 6 (7,8). impaired astrocytic function is regarded as a critical issue implicated in neuroinflammation (9); however, the underlying molecular mechanism remains obscure.…”

“…it has been well documented that aQP4 is intimately involved in the modulation of astrocyte function (12), but the majority of knowledge on the transporter is limited to water balance (13), glial scar formation (14) and neuroexcitation (15). little focus has been placed on the area of neuroinflammation until recently (9). as found by manley et al (16), aQP4 deletion attenuates AQP4-knockout alleviates the lipopolysaccharide-induced inflammatory response in astrocytes via SPHK1/MAPK/AKT signaling inflammation-related brain edema, providing a novel perspective on aQP4 in the management of neuroinflammation.…”

Yixinshu ameliorates hippocampus abnormality induced by heart failureviathe PPARγ signaling pathway

“…Aquaporin-4 (AQP4) is a water channel protein that can reconcile the homeostasis of water in the BBB. 16,17 Neuro-inammation is a hallmark that induces alterations in brain structure and function in major depressive disorders.…”