Expression of the Astrocyte Water Channel Aquaporin-4 in the Mouse Brain

Abstract

Aquaporin-4 (AQP4) is a bidirectional water channel that is found on astrocytes throughout the central nervous system. Expression is particularly high around areas in contact with cerebrospinal fluid, suggesting that AQP4 plays a role in fluid exchange between the cerebrospinal fluid compartments and the brain. Despite its significant role in the brain, the overall spatial and region-specific distribution of AQP4 has yet to be fully characterized. In this study, we used Western blotting and immunohistochemical techniques to characterize AQP4 expression and localization throughout the mouse brain. We observed AQP4 expression throughout the forebrain, subcortical areas, and brainstem. AQP4 protein levels were highest in the cerebellum with lower expression in the cortex and hippocampus. We found that AQP4 immunoreactivity was profuse on glial cells bordering ventricles, blood vessels, and subarachnoid space. Throughout the brain, AQP4 was expressed on astrocytic end-feet surrounding blood vessels but was also heterogeneously expressed in brain tissue parenchyma and neuropil, often with striking laminar specificity. In the cerebellum, we showed that AQP4 colocalized with the proteoglycan brevican, which is synthesized by and expressed on cerebellar astrocytes. Despite the high abundance of AQP4 in the cerebellum, its functional significance has yet to be investigated. Given the known role of AQP4 in synaptic plasticity in the hippocampus, the widespread and region-specific expression pattern of AQP4 suggests involvement not only in fluid balance and ion homeostasis but also local synaptic plasticity and function in distinct brain circuits.

SUR1‐TRPM4 and AQP4 form a heteromultimeric complex that amplifies ion/water osmotic coupling and drives astrocyte swelling

“…Sections immunolabeled for TRPM4 or SUR1 were co‐immunolabeled for AQP4, an astrocyte‐specific marker. Cerebellar granule cell layer AQP4 labeling was uniformly present across the astrocyte plasmalemma (Figure b,c), as previously reported (Hubbard, Hsu, Seldin, & Binder, ). In the injured granule cell layer, AQP4 closely co‐localized with TRPM4 (Figure b) and SUR1 (Figure c).…”

An Efficient Platform for Astrocyte Differentiation from Human Induced Pluripotent Stem Cells

“…Compared with NPCs or excitatory neurons (h NGN2 -induced neurons) (Brennand et al., 2015), hiPSC-astrocytes expressed GFAP (Ludwin et al., 1976), S100β (Ludwin et al., 1976), VIM (Schnitzer et al., 1981), AQU4 (Hubbard et al., 2015), ACSBG1 (Chaboub and Deneen, 2013), and APOE (Boyles et al., 1985) by qPCR (Figure 1D), although expression levels between individual hiPSC-astrocytes and primary astrocyte lines varied substantially. In addition, hiPSC-astrocytes expressed low levels of the neuronal markers TUJ1 , MAP2AB , RELN , and CACNA1C (Figure 1E).…”

Aquaporin‐4 expression dynamically varies after acute spinal cord injury‐induced disruption of blood spinal cord barrier in rats

“…Among all aquaporins, AQP4 is the most abundant one in the CNS . AQP4 was first discovered in the serum of patients with neuromyelitis optica (NMO), and besides NMO, AQP4‐IgG has been found to be related with many other types of CNS demyelinating diseases, such as multiple sclerosis and Balo's concentric sclerosis.…”