Primary Cilia of Supraoptic Nucleus Regulate Drinking and Blood pressure

Abstract

Fluid intake is tightly related to blood pressure control through balance between electrolytes and water in the body. Virtually, every mammalian cell is equipped with a primary cilium, a cell surface protrusion that is thought to act as a sensory organelle. However, the contribution of primary neuronal cilia to cardiovascular regulation and fluid homeostasis has not been addressed. We hypothesized that primary neuronal cilia contribute to the control of fluid intake and blood pressure. For this, we first examined the length of primary neuronal cilia in the brain nuclei that contribute to osmolarity and cardiovascular regulation in 3‐week DOCA‐salt treated mice vs sham controls (n=5/group). Cilia length was examined by immunostaining a ciliary protein, adenylate cyclase 3 (AC3), followed by confocal 3D reconstruction, and quantification by IMARIS imaging analysis software. We found changes in cilia length in a number of brain nuclei of DOCA‐salt mice. The supraoptic nucleus (SON), a key brain nucleus in the regulation of osmolarity and fluid homeostasis, displayed the most significant changes in cilia length (average primary cilia: 7.46±□□□□□m in DOCA‐salt mice vs 6.76±□□□□□m in sham, p=0.0509). Moreover, the number of primary cilia that are over 10□□m was significantly increased in the SON of DOCA‐salt mice by 8% (p=0.0114). On the other hand, the number of cilia that are 4–5□□m in length was significantly decreased in the SON of DOCA‐salt mice (11.73±1.70%) compared to sham controls (18.73±2.02%, p=0.0385). Next, we assessed the relevance of SON cilia by targeting the ift88 gene which encodes a protein necessary for the formation of cilia. For this, we performed targeted stereotaxic injection of AAV‐Cre into the SON of IFT88flox/flox mice. We found that disruption of SON ift88 (AAV‐Cre group had a 38% ift88 expression level relative to AAV‐GFP control group) caused impairment in water intake in response to 24h water deprivation (30min water intake: 0.78±0.06 ml in AAV‐Cre vs 1.07±0.08 ml in AAV‐GFP, p=0.0129) without affecting total daily water and food consumption. Moreover, ift88 deletion in SON increased systolic blood pressure (133.7±1.71 mmHg vs 115.8±2.33 in AAV‐GFP, p=0.0008) without altering heart rate. Our data demonstrate the importance of primary cilia in the SON in the regulation of water intake and blood pressure. We speculate that primary neuronal cilia may function as part of environmental surveillance system in the brain that ensures cardiovascular homeostasis.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.