Role of hyperpolarization-activated cyclic nucleotide-gated channels in aging bladder phenotype

Singh, Nishant; Zabbarova, Irina; Ikeda, Youko; Chermansky, Christopher; Yoshimura, Naoki; Tyagi, Pradeep

doi:10.1016/j.lfs.2021.120203

Cited by 4 publications

(3 citation statements)

References 41 publications

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“…Response heterogeneity has been previously associated with alterations in ion channel expression, as variances about mean responses to adrenergic stimuli in strip studies paralleled decreasing expression of Hcn1 , encoding the hyperpolarization‐activated cyclic nucleotide‐gated channel 1 protein (Hardy et al, 2021 ), which has previously been shown to play an important role in adrenergic detrusor tension control with aging in B6 mice (Al‐Naggar et al, 2019 ; Lemtiri‐Chlieh et al, 2022 ; Mader et al, 2018 ; Singh et al, 2022 ). Apart from tissue‐level responses, heterogeneity is also exhibited in response to the stressor of cystometry.…”

Section: Changes With Aging Along the Brain–bladder ...mentioning

confidence: 93%

Aging and urinary control: Alterations in the brain–bladder axis

Hardy,

Korstanje

2023

Aging Cell

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Age‐associated alterations in bladder control affect millions of older adults, with a heavy burden added to families both economically and in quality of life. Therapeutic options are limited with poor efficacy in older adults, lending to a growing need to address the gaps in our current understanding of urinary tract aging. This review summarizes the current knowledge of age‐associated alterations in the structure and function of the brain–bladder axis and identifies important gaps in the field that have yet to be addressed. Urinary aging is associated with decreased tissue responsiveness, decreased control over the voiding reflex, signaling dysfunction along the brain–bladder axis, and structural changes within the bladder wall. Studies are needed to improve our understanding of how age affects the brain–bladder axis and identify genetic targets that correlate with functional outcomes.

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Section: Changes With Aging Along the Brain–bladder ...mentioning

confidence: 93%

Aging and urinary control: Alterations in the brain–bladder axis

Hardy,

Korstanje

2023

Aging Cell

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“…The bladder participates in homeostasis via endocrine and stretch-mediated urine reabsorption [9,51,52,54,55] to match with the constant-but-slow rate of urine production during sleep [56]. The multicellular layer of the urothelium [57] lining the bladder is a highly metabolically active [12] multifunctional tissue for monitoring bladder distension [58] and signaling constitutional changes in urine [53,59,60] to the detrusor, micturition centers, and the immune system [61]. The top layer of the urothelium relies on the restricted transcellular permeability [62] of the umbrella cells endowed with the asymmetric membrane on the apical side to survive the low pH and three-fold-higher osmotic pressure of urine [9,63] than the serum (Figure 1).…”

Section: The Urinary Bladdermentioning

confidence: 99%

SWOT and Root Cause Analyses of Antimicrobial Resistance to Oral Antimicrobial Treatment of Cystitis

Tyagi,

Stewart

et al. 2024

Antibiotics

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Nearly 150 million cases of urinary tract infections (UTIs) are reported each year, of which uncomplicated cystitis triggers > 25% of outpatient prescriptions of oral antimicrobial treatment (OAT). OAT aids immune cells infiltrating the urothelium in eliminating uropathogens capable of invading the urothelium and surviving hyperosmotic urine. This self-evident adaptability of uropathogens and the short interval between the introduction of Penicillin and the first report of antimicrobial resistance (AMR) implicate AMR as an evolutionary conserved heritable trait of mutant strains selected by the Darwinian principle to survive environmental threats through exponential proliferation. Therefore, AMR can only be countered by antimicrobial stewardship (AMS) following the principle of the five Ds—drug, dose, duration, drug route, and de-escalation. While convenient to administer, the onset of the minimum inhibitory concentration (MIC) for OAT in urine leaves a window of opportunity for uropathogens to survive the first contact with an antimicrobial and arm their descendant colonies with AMR for surviving subsequent higher urine antimicrobial levels. Meanwhile, the initial dose of intravesical antimicrobial treatment (IAT) may be well above the MIC. Therefore, the widespread clinical use of OAT for cystitis warrants an analysis of the strengths, weaknesses, opportunity, and threats (SWOTs) and a root cause analysis of the AMR associated with OAT and IAT.

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“…The bladder participates in homeostasis via endocrine and stretch mediated urine reabsorption [7,28,29,31,32] , thereby the bladder acts as a backstop to the constant but slow rate of urine production by the kidneys during sleep to prevent nocturnal voiding episodes (nocturia), a symptom of cystitis [33]. The bladder is lined by a multicellular layer of urothelium [34], a highly metabolically active [35] multifunctional tissue that monitors bladder distension [36], signals constitutional changes to the detrusor, micturition centers and the immune system [37]. Umbrella cells rely on restricted transcellular permeability [38] of the asymmetric membrane on the apical side to survive the low pH and threefold higher osmotic pressure of urine [7,39] than the serum (Figure 1).…”

Section: The Urinary Bladdermentioning

confidence: 99%

SWOT and Root Cause Analysis of Antimicrobial Resistance to Oral Antimicrobial Treatment of Cystitis

Tyagi,

Stewart

et al. 2024

Preprint

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Out of a worldwide annual incidence of ~150 million cases for urinary tract infection (UTI), >25% of outpatient prescriptions of oral antimicrobial treatment (OAT) are for cystitis not complicated by sepsis. OAT aids the immune cells infiltrating urothelium to eliminate uropathogens attaching and invading urothelium amidst hyperosmotic urine. This adaptability of uropathogens and the short interval between Penicillin sale and the first antimicrobial resistance (AMR) report suggests that AMR is a 3.8 billion years old evolutionary conserved heritable trait of surviving environmental threats through exponential proliferation of mutant strains selected by Darwinian principle. Therefore, OAT success with minimal AMR can be ensured by antimicrobial stewardship (AMS) following the principle of 5Ds -drug, dose, duration, drug-route, and de-escalation. While convenient to administer, the onset of minimum inhibitory concentration (MIC) for OAT in urine is a window of opportunity for uropathogens to survive the first contact with OAT and the descendant colonies armed with AMR are likely to survive subsequent higher urine OAT levels. Meanwhile, intravesical antimicrobial treatment (IAT) delivers the first strike well above MIC. The root cause analysis of AMR dovetails with the strengths, weaknesses, opportunity, and threat (SWOT) analysis of OAT in this interdisciplinary review.

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Role of hyperpolarization-activated cyclic nucleotide-gated channels in aging bladder phenotype

Cited by 4 publications

References 41 publications

Aging and urinary control: Alterations in the brain–bladder axis

Aging and urinary control: Alterations in the brain–bladder axis

SWOT and Root Cause Analyses of Antimicrobial Resistance to Oral Antimicrobial Treatment of Cystitis

SWOT and Root Cause Analysis of Antimicrobial Resistance to Oral Antimicrobial Treatment of Cystitis

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