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: