Unique expression and localization of aquaporin‐ 4 and aquaporin‐9 in murine and human neural stem cells and in their glial progeny

Abstract

Aquaporins (AQP) are water channel proteins that play important roles in the regulation of water homeostasis in physiological and pathological conditions. AQP4 and AQP9, the main aquaporin subtypes in the brain, are expressed in the adult forebrain subventricular zone (SVZ), where neural stem cells (NSCs) reside, but little is known about their expression and role in the NSC population, either in vivo or in vitro. Also, no reports are available on the presence of these proteins in human NSCs. We performed a detailed molecular and phenotypical characterization of different AQPs, and particularly AQP4 and AQP9, in murine and human NSC cultures at predetermined stages of differentiation. We demonstrated that AQP4 and AQP9 are expressed in adult murine SVZ-derived NSCs (ANSCs) and that their levels of expression and cellular localization are differentially regulated upon ANSC differentiation into neurons and glia. AQP4 (but not AQP9) is expressed in human NSCs and their progeny. The presence of AQP4 and AQP9 in different subsets of ANSC-derived glial cells and in different cellular compartments suggests different roles of the two proteins in these cells, indicating that ANSC-derived astrocytes might maintain in vitro the heterogeneity that characterize the astrocyte-like cell populations in the SVZ in vivo. The development of therapeutic strategies based on modulation of AQP function relies on a better knowledge of the functional role of these channels in brain cells. We provide a reliable and standardized in vitro experimental model to perform functional studies as well as toxicological and pharmacological screenings. V V C 2005 Wiley-Liss, Inc.

AQP4 knockout impairs proliferation, migration and neuronal differentiation of adult neural stem cells

“…AQP4 is one of the predominant aquaporins in ANSCs as well as in astrocytes in the brain (Cavazzin et al, 2006). In the present study, we showed that AQP4 knockout inhibited proliferation, migration and neuronal differentiation of ANSCs in vitro.…”

“…In the damaged brain, adult neurogenesis is also found in the neocortex, striatum, amygdala and substantia nigra (Gould, 2007) where AQP4 has a high level of expression. Finally, it is reported that AQP4 is the main subtype of aquaporin in adult neural stem cells (ANSCs) (Cavazzin et al, 2006;La Porta et al, 2006;Schwartz et al, 2005).…”

Requirement of AQP4 for Antidepressive Efficiency of Fluoxetine: Implication in Adult Hippocampal Neurogenesis

“…Thus, AQP4 may participate in adult neurogenesis by regulating astrocytic function. More importantly, AQP4 is the main subtype of AQP in ANSCs (Cavazzin et al, 2006). However, it is unclear whether AQP4 involves adult hippocampal neurogenesis.…”

GABAA Receptor Signaling Induces Osmotic Swelling and Cell Cycle Activation of Neonatal Prominin+ Precursors

“…In cells expressing these channels, the direction of the water flux is determined only by the osmotic gradient. Underscoring the importance of the process of water exchange in these populations, it was found that a lack of aquaporin 4, expressed in ependymal cells and in neurosphere precursors derived from adult stem cells, leads to a functional and structural breakdown of the ependyma and to an impairment of multiple aspects of neural precursor growth in vitro [40]. Therefore, our observations that GABA A R activation promotes osmotic swelling in prominin þ precursors suggest the possibility that GABA participates in the regulation of osmotic tension in this specialized subset of precursors.…”