Aquaporins in the Spinal Cord

Abstract

Aquaporins (AQPs) are water channel proteins robustly expressed in the central nervous system (CNS). A number of previous studies described the cellular expression sites and investigated their major roles and function in the brain and spinal cord. Among thirteen different mammalian AQPs, AQP1 and AQP4 have been mainly studied in the CNS and evidence has been presented that they play important roles in the pathogenesis of CNS injury, edema and multiple diseases such as multiple sclerosis, neuromyelitis optica spectrum disorders, amyotrophic lateral sclerosis, glioblastoma multiforme, Alzheimer's disease and Parkinson's disease. The objective of this review is to highlight the current knowledge about AQPs in the spinal cord and their proposed roles in pathophysiology and pathogenesis related to spinal cord lesions and injury.

Keywords: aquaporin; astrocytes; central nervous system; endothelial cells; neurons; peripheral nerve; spinal cord.

Figure 1

AQP1 expression in the spinal cord. AQP1 was strongly expressed at laminae I and II of the dorsal horn with decreasing signal intensity at the medial edges of dorsal horns up to lamina V (A,D); A fraction of the AQP1 signal belonged to unmyelinated neuronal cells (B) protruding from dorsal root ganglion to the superficial laminae of dorsal horns which axons build up peripheral sensory fibers (C); Illustration of AQP1 expression in the spinal cord cross-section (D); AQP1 labeling in the white matter was rather infrequent and found in proximity to the glia limitans (E) most likely belonging to small arterioles furcating from the arterial vasocorona (F,G). Panels A, B, E and F are modified from Oklinski et al. [21]. The blue signal in panels B and F represents 4′,6-diamidino-2-phenylindole (DAPI) staining of the nuclei; AQP1, aquaporin 1; PERIPH, peripherin and RECA, rat endothelial cell antigen-1. Colocalization indicated by arrows. AQP1 is indicated in red on panels C, D and G. AQP4 is drawn in green on panel G. White arrows in B and F.

Figure 2

AQP4 expression in the spinal cord. AQP4 was abundantly expressed across the whole spinal cord with markedly higher intensity in the superficial lamina of dorsal horns, verges of ventral horns, glia limitans and surroundings of blood vessels (A); In the gray matter, protoplasmatic astrocytes AQP4 expression represents a polarized pattern with the highest intensity in the astrocytes foot processes encircling capillaries (B,C) and weaker labeling in processes belonging to the tripartite synapse (C); In the white matter, fibrous astrocytes AQP4 expression is observed along the cell membrane (D,E); Illustrations of AQP4 expression in the spinal cord (C,E) markings in green illustrate AQP4. The blue signal in panels B and D represents DAPI staining of the nuclei. Immunoperoxidase staining of AQP4 (A) and immunofluorescence images (B,D) are modified from Oklinski et al. [21]. AQP4, aquaporin 4; GS, glutamate synthase.