School of Podiatric Medicine Publications

A systematic study of the distribution and expression of aquaporin water channels in normal adult human brain

Document Type

Article

Publication Date

8-13-2025

Abstract

Backgrounds: Water regulation in the central nervous system (CNS) is very important to maintain normal neurophysiological homeostasis and intracranial pressure, as well as during neuropathological conditions. Not only because of the rigidity and limited mobility of the brain encasement, but also the need to maintain an appropriate osmotic balance across the various fluid-filled brain compartments for normal neurological functions. Aquaporins (AQPs), a family of non-energy dependent, bidirectional water transport protein channels play a crucial role in the maintenance of water and electrolyte balance in the human brain and their distribution and expression in regions of the brain need to be characterized to definitively certify and associate their pathogenic role in neuropathological disorders.

Results: We carried out a detailed and systematic study of aquaporin-1 (AQP1), aquaporin-4 (AQP4) and aquaporin-9 (AQP9) expression in neurologically normal, autopsy brain tissues from nine patients. Interestingly, AQP1 immunoreactivity was not observed in the ependymal cell layer and cortical gray matter (GM) despite glial fibrillary acidic protein (GFAP) immunoreactive astrocytes in these regions. However, AQP1 was preferentially but not exclusively expressed in the white matter (WM) regions of the CNS, including the subcortical cerebral and cerebellar WM, brainstem, spinal cord, and choroid plexus. AQP4 immunolabeling was detected in both GM and WM regions of the CNS examined with enhanced expression in the upper and deeper layers of the cerebral cortex, while AQP9 immunoreactivity was only detected in the choroid plexus co-localizing with AQP1.

Conclusions: This is the first detailed and sequential study of AQP water transport channels in all regions of the human brain. The data affirm the anatomical locations, corresponding to the physiological functions of the three major AQP (AQP1, AQP4, and AQP9) water transport protein channels found in the adult human brain.

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Publication Title

Journal of neurology

DOI

10.1007/s00415-025-13304-9

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