Laminar-specific and developmental expression of aquaporin-4 in the mouse hippocampus

Abstract

Mice deficient in the water channel AQP4 demonstrate increased seizure duration in response to hippocampal stimulation as well as impaired extracellular K+ clearance. However, the expression of AQP4 in the hippocampus is not well described. In this study, we investigated i) the developmental, laminar and cell-type specificity of AQP4 expression in the hippocampus; ii) the effect of Kir4.1 deletion on AQP4 expression; and iii) performed Western blot and RT-PCR analyses. AQP4 immunohistochemistry on coronal sections from WT or Kir4.1-/- mice revealed a developmentally-regulated and laminar-specific pattern, with highest expression in the CA1 stratum lacunosummoleculare (SLM) and the molecular layer (ML) of the dentate gyrus (DG). AQP4 was colocalized with the glial markers GFAP and S100ß in the hippocampus, and was also ubiquitously expressed on astrocytic endfeet around blood vessels. No difference in AQP4 immunoreactivity was observed in Kir4.1-/- mice. Electrophysiological and postrecording RT-PCR analyses of individual cells revealed that AQP4 and Kir4.1 were co-expressed in nearly all CA1 astrocytes. In NG2 cells, AQP4 was also expressed at the transcript level. This study is the first to examine subregional AQP4 expression during development of the hippocampus. The strikingly high expression of AQP4 in the CA1 SLM and DG ML identifies these regions as potential sites of astrocytic K+ and H2O regulation. These results begin to delineate the functional capabilities of hippocampal subregions and cell types for K+ and H2O homeostasis, which is critical to excitability and serves as a potential target for modulation in diverse diseases.

Anti-edema effect of melatonin on spinal cord injury in rats

“…AQP4, as a member of the AQP family, is widely expressed in the nervous system. Previous studies showed the colocalization of AQP4 with GFAP in double labeling by using confocal microscopy 37,38 . Badaut et al reported that AQP4 was found in astrocyte foot processes around capillaries in the human brain 39 .…”

Regulation of neurovascular coupling in autoimmunity to water and ion channels

“…Kir4.1 channel expression and function are no different in AQP4 KO mice [81, 82], and inhibition or knockdown of Kir4.1 causes no change in the water permeability of AQP4 [82]. Also, no change in AQP4 expression has been observed in Kir4.1 KO mice [83]. However, AQP4 may support K + buffering by altering the concentration in the extracellular space.…”

Cytoprotective effects of growth factors: BDNF more potent than GDNF in an organotypic culture model of Parkinson's disease

“…The distribution of astrocyte AQP4 differs significantly within the brain, suggesting that AQP4 has multiple physiological roles (20,21,309). To date, this heterogeneity is not well described.…”