Attenuation of peripheral salt taste responses and local immune function contralateral to gustatory nerve injury: effects of aldosterone

Abstract

Dietary sodium restriction coupled with axotomy of the rat chorda tympani nerve (CTX) results in selectively attenuated taste responses to sodium salts in the contralateral, intact chorda tympani nerve. Converging evidence indicates that sodium deficiency also diminishes the activated macrophage response to injury on both the sectioned and contralateral, intact sides of the tongue. Because a sodium-restricted diet causes a robust increase in circulating aldosterone, we tested the hypothesis that changes in neurophysiological and immune responses contralateral to the CTX could be mimicked by aldosterone administration instead of the low-sodium diet. Taste responses in rats with CTX and supplemental aldosterone for 4-6 days were similar to rats with CTX and dietary sodium restriction. Responses to sodium salts were as much as 50% lower compared with sham-operated and vehicle-supplemented rats. The group-related functional differences were eliminated with lingual application of amiloride, suggesting that a major transduction pathway affected was through epithelial sodium channels. Consistent with the functional results, few macrophages were observed on either side of the tongue in rats with CTX and aldosterone. In contrast, macrophages were elevated on both sides of the tongue in rats with CTX and the vehicle. These results show that sodium deficiency or administration of aldosterone suppresses the immune response to neural injury, resulting in attenuation of peripheral gustatory function. They also show a potential key link among downstream consequences of sodium imbalance, taste function, and immune activity.

Fig. 1.

Integrated responses from the chorda tympani nerve to a concentration series of NaCl and to 500 mM NH₄Cl in a rat receiving a chorda tympani nerve section on the contralateral side and supplemental aldosterone (CTX + Aldo; top), sham surgery and aldosterone (Sham + Aldo; middle), and sham with a saline vehicle (Sham + Veh; bottom). Increasing NaCl concentration produces an increase in chorda tympani nerve response in Sham + Aldo and Sham + Veh rats, so that the steady-state response to 500 mM NaCl is similar to the response to 500 mM NH₄Cl. Increasing concentration of NaCl in CTX + Aldo rats saturates at ∼100 mM NaCl, which is about 50% of the steady-state response to 500 mM NH₄Cl. Scale bar = 1 min.

Fig. 2.

A: mean ± SE responses of the chorda tympani nerve to a concentration series of NaCl in rats receiving a chorda tympani nerve section on the contralateral side and given aldosterone (CTX + Aldo) or a saline vehicle (CTX + Veh), or rats with a sham surgery and given aldosterone (Sham + Aldo) or a saline vehicle (Sham + Veh). Water was used as the solvent for the stimuli and the rinse. These data are compared with data in which rats sustained a chorda tympani nerve section on the contralateral side and then fed a low-NaCl diet (CTX + Sodium Restriction). Means from CTX + Veh, Sham + Aldo, and Sham + Veh were similar to each other (P > 0.05), but all were significantly greater than those in CTX + Aldo and CTX + Sodium Restriction rats (P < 0.05). B: mean ± SE responses of the chorda tympani nerve to a concentration series of NaCl mixed in amiloride in the same rats shown as in A. Amiloride was used as the solvent for the stimuli and the rinse. None of the means differed from each other when stimuli were mixed in amiloride (P > 0.05).

Fig. 3.

Means ± SE responses of the chorda tympani nerve to a concentration series of sodium acetate (NaAc; A), KCl (B), or NH₄Cl (C) in rats receiving a chorda tympani nerve section on the contralateral side and given aldosterone (CTX + Aldo) or a saline vehicle (CTX + Veh), or rats with a sham surgery and given aldosterone (Sham + Aldo) or a saline vehicle (Sham + Veh). These data are compared with data in which rats had a chorda tympani nerve section on the contralateral side and then fed a low-NaCl diet (CTX + Sodium Restriction).

Fig. 4.

ED1⁺-activated macrophages (brown immunoreactivity) at day 2 postsectioning. There were few macrophages on the CTX (A) or intact (B) sides of the tongue or within fungiform papillae (C) after sham sectioning and aldosterone (Sham + Aldo). Following CTX and vehicle (CTX + Veh), activated macrophages were abundant in the submucosa of the CTX (D) and intact (E) sides of the tongue and in intact fungiform papillae (F). Aldosterone prevented the macrophage response to nerve injury on the sectioned side (CTX + Aldo; G), the intact side (H), and in intact fungiform papillae (I). Stars in C, F, and I indicate taste buds. Scale bar = 30 μm.

Fig. 5.

Analysis of activated macrophages (percentage of ED1/standard area). Solid bars represent macrophage levels on the CTX side of the tongue, or the right side in sham-sectioned groups. Hatched bars show levels measured on the contralateral, uninjured side. Macrophages remained low in groups receiving sham CTX, whether pumps administered vehicle (Sham + Veh) or aldosterone (Sham + Aldo). The macrophage response to nerve section also remained at baseline levels on both sides of the tongue in sodium-restricted rats (CTX + Na+ Restriction), as expected. CTX dramatically increased activated macrophages on both sides of the tongue (CTX + Veh) (P < 0.001 vs. values from each of the other groups), but aldosterone prevented this response (CTX + Aldo).