Aquaporin-4 Localization in Terminal Glial Cells of Human Mechanosensory Corpuscles: An Immunohistochemical Study of Penile Tissues

Aquaporin-4 (AQP4), the predominant water channel in the central nervous system, has been extensively characterized in astroglia, but its presence in peripheral mechanoreceptive end-organs remains unknown. We investigated AQP4 localization in human mechanosensory corpuscles using formalin-fixed, paraffin-embedded penile tissues from 11 adult cadavers and 12 surgical prepuces. Single and double immunohistochemistry was performed in serial sections with a comprehensive battery of antibodies targeting axons (neurofilaments, neuron-specific enolase [NSE], protein gene product 9.5 [PGP9.5], synaptophysin), glial cells (S100, nestin, nerve growth factor receptor [NGFR], vimentin, Wilms’ tumor 1 [WT1], growth-associated protein 43 [GAP43]), perineurial and endoneurial cells (α-smooth muscle actin [α-SMA], epithelial membrane antigen [EMA], glucose transporter 1 [Glut-1], CD34), and extracellular matrix components (collagen type IV [COLIV]). AQP4 immunoreactivity was consistently observed in the terminal glial cells (TGCs) of all types of mechanosensory corpuscles across all penile regions examined, including Meissner, genital, Krause, and Pacinian corpuscles. Outer-core lamellar cells of Pacinian corpuscles also exhibited AQP4 expression. The AQP4 + mechanosensory corpuscles exhibited immunohistochemical profiles consistent with the established marker patterns of sensory corpuscles (S100 + /WT1 + /vimentin + /nestin + /Gap-43 + /NGFR + TGCs; synaptophysin + /neurofilaments + /PGP9.5 + /NSE + axons; CD34 + intermediate layer; EMA + /Glut-1 + /vimentin + /COLIV + /NGFR + /Gap-43 + outer core; COLIV + extracellular matrix). Beyond sensory corpuscles, AQP4 was present in Schwann cells of nerve bundles and inconsistently in vascular endothelium. These findings provide the first evidence that AQP4 is a molecular constituent of TGCs in human mechanosensory corpuscles, suggesting roles in local water–ion homeostasis or other non-transporting functions of AQP4, and warranting further investigation of its biological significance in low-threshold mechanoreceptor end-organs: