Structural Reconstruction of the Perivascular Space in the Adult Mouse Neurohypophysis during an Osmotic Stimulation

Abstract

Oxytocin (OXT) and arginine vasopressin (AVP), neuropeptides in the neurohypophysis (NH), control lactation and body fluid homeostasis, respectively. Hypothalamic neurosecretory neurons project their axons from the supraoptic and paraventricular nuclei to the NH to make contact with the vascular surface and release OXT and AVP. The neurohypophysial vascular structure is unique, because it has a wide perivascular space between the inner and outer basement membranes. However, the significance of this unique vascular structure remains unclear; therefore, we aimed to elucidate the functional significance of the perivascular space and its activity-dependent changes during salt loading in adult mice. Our results revealed that pericytes were the main resident cells and defined the profile of the perivascular space. Moreover, pericytes sometimes extended their cellular processes or "perivascular protrusions" into neurohypophysial parenchyma between axonal terminals. The vascular permeability of low-molecular-weight (LMW) molecules was higher at perivascular protrusions than at the smooth vascular surface. Axonal terminals containing OXT and AVP were more likely to localize at perivascular protrusions than at the smooth vascular surface. Chronic salt loading with 2% NaCl significantly induced prominent changes in the shape of pericytes, and increased the number of perivascular protrusions and surface area of the perivascular space together with elevations in the vascular permeability of LMW molecules. Collectively, these results indicate that the perivascular space of the NH acts as the main diffusion route for OXT and AVP, and changes in the shape of pericytes and perivascular reconstruction occur in response to increased demand for neuropeptide release.

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