Lithium Induces Cilia Expression in Renal Intercalated Cells

Abstract

Listen

Translate article

Lithium remains a first line drug for treatment of bipolar disorder (BD). It has demonstrated efficiency for the prevention of recurrence of mood episodes, and also as an enhancement strategy in major depressive disorder. Current research and a growing number of publications predict a wider role for Li in the coming years for various neurological disorders. One major limitation of Li treatment is the short‐ and long‐term adverse effects it has on the kidney in a subpopulation of its recipients. Up to 40% of Li receiving patients report various degrees of acute increase in urine production ‐ Nephrogenic Diabetes Insipidus (NDI). Long‐term Li treatment has a more severe side effect known as Chronic Kidney Disease (CKD), characterized by reduced glomerular filtration rate, interstitial nephritis, renal fibrosis, microcyst formation, ultimately leading to end‐stage renal disease. Renal cyst formation has also been implicated as a ciliopathy in polycystic kidney disease. Here, we studied the effect of Li on cilia in a mouse model treated for 3 months. Using immuno‐fluorescence, we imaged cilia in 16 μm thick sections of paraformaldehyde‐fixed mouse kidney. Cilia were labeled using an antibody against acetylated alpha‐tubulin. The 3D confocal images were deconvolved using Volocity software, and ciliary length from control and Li‐treated animals was measured in different tubule segments. In the different tubule segments, the mean length of cilia was different, but was not affected by Li except in the cortical collecting duct, where Li treatment significantly increased ciliary length from 6.6±0.4 μm to 7.7±0.3 μm. Collecting ducts are composed of two major cell types, intercalated (ICs) and principal cells (PCs), which were identified by the expression of cell type‐specific markers, the vacuolar proton‐pumping ATPase and aquaporin‐2, respectively. Among epithelial cells in the kidney, ICs are the only cell type that was never shown to express primary cilia. Remarkably, we found that Li treatment induces cilia expression in ICs. Li treatment is known to increase the ratio of ICs to PCs. Whether bona fide ICs are growing cilia de novo in response to Li treatment, or we are detecting PCs that have converted into ICs but still have a residual cilium that is not completely reabsorbed, remains to be elucidated.Support or Funding InformationNational Institutes of Health Grant DK096586 (D. Brown)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.