Osmotic stimulation disrupts interleukin-1 β expression and upregulates CD206 and aquaporine-4 in the adult mouse neurohypophysis.

The neurohypophysis (NH) is a specialized neuro-glial interface where neuronal, glial, and vascular elements coordinate neuroendocrine secretion and immune signalling. Its intrinsic plasticity supports adaptation to osmotic and inflammatory stress. Osmotic challenges, such as salt loading, induce structural and functional remodelling within the NH, engaging both microglia and pituicytes. To determine these adaptive processes, we examined the effects of 4 and 8 days of salt loading (2% NaCl) on cellular plasticity in the mouse NH. Pituicyte morpho-functional remodelling was assessed by immunohistochemistry using specific markers (GFAP, AQP4), while microglial activation and polarization were evaluated using Iba1 and CD206. These analyses were complemented by Western blot experiments, including the measurement of the pro-inflammatory cytokine IL-1β. Physiological parameters such as fluid intake, body weight, plasma osmolality and haematocrit were also evaluated. Immunohistochemical analysis revealed a marked morphological transformation of microglia from a ramified to an amoeboid phenotype following osmotic stimulation. Western blot analysis showed stable Iba1 expression, indicating that this activation occurred without microglial proliferation. After 8 days of salt loading, CD206 expression significantly increased, accompanied by a decrease in IL-1β, suggesting polarization of microglia toward an anti-inflammatory M2 profile. Additionally, GFAP expression decreased, whereas AQP4 expression increased, particularly in the perivascular region. Physiologically, salt loading increased fluid intake and haematocrit, reduced body weight, while plasma osmolality remained unchanged. Together, these findings indicate coordinated neuroimmune remodelling in the NH. The shift toward an anti-inflammatory glial profile and increased AQP4 expression likely represents an adaptive mechanism that supports tissue homeostasis during hyperosmotic stress.