Biology subjects

Keil Stietz, K.

Publications and source records attributed to Keil Stietz, K..

2 recordsLinked to original sources

bioRxiv2026

A Neuroendocrine Circuit That Suppresses Excretion and Pelvic Pain During Activity

Mate-seeking during peak sexual receptivity is tightly coupled with exploratory movement, a process made more efficient by transient suppression of excretion. Here, we define a functional hypothalamic-hindbrain circuit in mice that promotes locomotion while eliminating urination and defecation for hours. Chemogenetic stimulation of excitatory estrogen-melanocortin-responsive MC4R+ neurons in the ventrolateral ventromedial hypothalamus (VMHvl) effectively silences bladder and colonic visceral reflexes, even at noxious distension pressures, underscoring the potency of this anti-excretion circuit. Pelvic sensations and excretion are restored only after ablating inhibitory GABAergic neurons in the Barringtons nucleus/locus coeruleus (BAR/LC) hindbrain region or after antagonizing endogenous endorphin signaling. Our study illustrates how a hormone-responsive brain node prioritizes movement over excretion and blunts pelvic discomfort, thereby optimizing an essential voluntary behavior for evolutionary fitness.

physiology↗

bioRxiv2026

PIEZO1-mediated mechanosensation links aging to bladder dysfunction

Aging is accompanied by profound changes in bladder function, leading to increased urinary frequency and incontinence that impair quality of life in humans and are recapitulated in mouse models. Bladder filling and emptying rely on precise mechanosensory feedback, yet how aging alters this sensory control remains unclear. PIEZO ion channels convert mechanical forces into cellular signals essential for bladder fullness sensation. Using inducible smooth-muscle specific Piezo1 deletion, we find that loss of Piezo1 attenuates aging-related bladder dysfunction. Dietary enrichment with margaric acid, a membrane-active fatty acid previously shown to inhibit PIEZO channels, reduced urinary dysfunction in aged mice. In humans, genotype-phenotype analyses reveal an association between a PIEZO1 gain-of-function variant and early-onset neuromuscular bladder dysfunction. Together, these findings define a smooth-muscle, PIEZO1-mediated mechanosensory basis for aging-related bladder dysfunction and introduce a non-invasive strategy for targeting PIEZO channels in vivo.

physiology↗