Male Akita mice develop signs of bladder underactivity independent of NLRP3 as a result of a decrease in neurotransmitter release from efferent neurons
| Autor: | Francis M. Hughes, Armand Allkanjari, Michael R. Odom, Jack E. Mulcrone, Huixia Jin, J. Todd Purves |
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| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | American Journal of Physiology-Renal Physiology. |
| ISSN: | 1522-1466 1931-857X |
| DOI: | 10.1152/ajprenal.00284.2022 |
| Popis: | Diabetic Bladder Dysfunction (DBD) is a prevalent diabetic complication that is recalcitrant to glucose control. Using the Akita mouse model (type 1) bred to be NLRP3+/+ or NLRP3-/-, we previously found that females (mild hyperglycemia) progress from an overactive to an underactive bladder phenotype and this progression was dependent on NLRP3-induced inflammation. Here we examined DBD in the male Akita (severe hyperglycemia) and found by urodynamics only a compensated underactive-like phenotype (increased void volume and decreased frequency but unchanged efficiency). Surprisingly, this phenotype was still present in the NLRP3-/- strain and so was not dependent on NLRP3 inflammasome-induced inflammation. Examining the cause of the compensated underactive-like phenotype, we assessed overall nerve density and afferent nerves (Aδ-fibers). Both were decreased in density during diabetes but denervation was absent in the diabetic NLRP3-/- strain so it was deemed unlikely to cause the underactive-like symptoms. Changes in bladder smooth muscle (BSM) contractility to cell depolarization and receptor activation were also not responsible as KCl (depolarizing agent), carbachol (muscarinic agonist) and α, β-methylene-ATP (purinergic agonist) elicited equivalent contractions in denuded bladder strips in all groups. However, electrical field stimulation revealed a diabetes-induced decrease in contractility that was not blocked in the NLRP3-/- strains suggesting that bladder compensated underactive-like phenotype in the male Akita is likely through a decrease in efferent neurotransmitter release. |
| Databáze: | OpenAIRE |
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