The urothelium of a hibernator: the American black bear

Abstract

The American black bear undergoes a 3–5 month winter hibernation during which time bears do not eat, drink, defecate, or urinate. During hibernation renal function (GFR) is 16–50% of normal but urine is reabsorbed across the urinary bladder (UB) urothelium thus enabling metabolic recycling of all urinary constituents. To elucidate the mechanism(s) whereby urine is reabsorbed, we examined the UBs of five nonhibernating wild bears using light, electron (EM), and confocal immunofluorescent (IF) microscopy–concentrating on two components of the urothelial permeability barrier – the umbrella cell apical membranes and tight junctions (TJ). Bear UB has the same tissue layers (serosa, muscularis, lamina propria, urothelia) and its urothelia has the same cell layers (basal, intermediate, umbrella cells) as other mammalians. By EM, the bear apical membrane demonstrated a typical mammalian scalloped appearance with hinge and plaque regions – the latter containing an asymmetric trilaminar membrane and, on IF, uroplakins Ia, IIIa, and IIIb. The umbrella cell TJs appeared similar to those in other mammals and also contained TJ proteins occludin and claudin - 4, and not claudin –2. Thus, we were unable to demonstrate urothelial apical membrane or TJ differences between active black bears and other mammals. Expression and localization of UT-B, AQP-1 and -3, and Na+, K+-ATPase on bear urothelial membranes was similar to that of other mammals. Similar studies of urothelia of hibernating bears, including evaluation of the apical membrane lipid bilayer and GAGs layer are warranted to elucidate the mechanism(s) whereby hibernating bears reabsorb their daily urine output and thus ensure successful hibernation.

Urea transport and clinical potential of urearetics

“…High protein diets can lead to high urinary urea concentrations, which may be carcinogenic in rat bladder (45). UT-B expression in the urothelium of the American black bear, an animal that hibernates, was similar to that found in other mammals (46). …”

Is electrolyte transfer across the urothelium important?: ICI‐RS 2015

“…The composition of the bladder wall of the black bear was reportedly remarkably similar in histology and ultrastructure to that of non‐hibernating mammals including humans. Interestingly, expression of urothelial proteins including uroplakins, occludin, and claudin was similar to other mammals, moreover, expression and localization of AQP‐1, AQP‐3, and Na + /K + ‐ATPase were not remarkably different . These observations coupled with the fact that the bear bladder also operates a filling/emptying cycle in non‐hibernating conditions raises the possibility that under certain (patho) physiological conditions, the human bladder might also modify urine composition.…”

“…Fry, unpublished data). Interestingly, the urothelium of the American black bear, a mammal that typically hibernates for 4–5 months and does not eat, drink, urinate, or defecate during that time but is known to produce and reabsorb urine in equal amounts daily, also expresses AQP‐1 and AQP‐3 …”

“…Interestingly, the urothelium of the American black bear, a mammal that typically hibernates for 4-5 months and does not eat, drink, urinate, or defecate during that time but is known to produce and reabsorb urine in equal amounts daily, 16 also expresses AQP-1 and AQP-3. 17 The cellular localization of AQPs in urothelial cells is an interesting indicator of functionality. AQP-2 and AQP-3 are located on the basolateral (not apical) membrane of umbrella cells and the plasma membranes of neighboring intermediate and basal cells in rat bladder.…”

“…Interestingly, expression of urothelial proteins including uroplakins, occludin, and claudin was similar to other mammals, moreover, expression and localization of AQP-1, AQP-3, and Na + /K + -ATPase were not remarkably different. 17 These observations coupled with the fact that the bear bladder also operates a filling/emptying cycle in nonhibernating conditions raises the possibility that under certain (patho) physiological conditions, the human bladder might also modify urine composition. Spector et al 17 noted that it is challenging to obtain bladder tissue from bears during the hibernation period, therefore limiting our ability to determine the functional expression of urothelial proteins and transport mechanisms during this time.…”