scholarly journals Social stress-induced bladder dysfunction: potential role of corticotropin-releasing factor

2009 ◽  
Vol 296 (5) ◽  
pp. R1671-R1678 ◽  
Author(s):  
Susan K. Wood ◽  
Madelyn A. Baez ◽  
Seema Bhatnagar ◽  
Rita J. Valentino
Keyword(s):  
Urinary Retention ◽  
Social Stress ◽  
Bladder Dysfunction ◽  
Bladder Capacity ◽  
Corticotropin Releasing Factor ◽  
Male Rats ◽  
Inhibitory Influence ◽  
Passive Behavior ◽  
Bladder Disorders

Psychological stress can impact on visceral function with pathological consequences, although the mechanisms underlying this are poorly understood. Here we demonstrate that social stress produces marked changes in bladder structure and function. Male rats were subjected to repeated (7 days) social defeat stress using the resident-intruder model. Measurement of the voiding pattern indicated that social stress produced urinary retention. Consistent with this, bladder size was increased in rats exposed to social stress. Moreover, this was negatively correlated to the latency to assume a subordinate posture, implying an association between passive behavior and bladder dysfunction. In vivo cystometry revealed distinct changes in urodynamic function in rats exposed to social stress, including increased bladder capacity, micturition volume, intermicturition interval, and the presence of non-micturition-related contractions, resembling overactive bladder. In contrast to social stress, repeated restraint (7 days) did not affect voiding, bladder weight, or urodynamics. The stress-related neuropeptide corticotropin-releasing factor (CRF) is present in spinal projections of Barrington's nucleus that regulate the micturition reflex and has an inhibitory influence in this pathway. Social stress, but not restraint, increased the number of CRF-immunoreactive neurons in Barrington's nucleus. Additionally, social stress increased CRF mRNA in Barrington's nucleus. Together, the results imply that social stress-induced CRF upregulation in Barrington's nucleus neurons results in urinary retention and, eventually, bladder dysfunction, perhaps as a visceral component of a behavioral coping response. This mechanism may underlie dysfunctional voiding in children and/or contribute to the development of stress-induced bladder disorders in adulthood.

scholarly journals A corticotropin-releasing factor receptor antagonist improves urodynamic dysfunction produced by social stress or partial bladder outlet obstruction in male rats

2013 ◽  
Vol 304 (11) ◽  
pp. R940-R950 ◽  
Author(s):  
Susan K. Wood ◽  
Kile McFadden ◽  
Tagan Griffin ◽  
John H. Wolfe ◽  
Stephen Zderic ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Social Stress ◽  
Bladder Outlet Obstruction ◽  
Outlet Obstruction ◽  
Bladder Capacity ◽  
Urinary Dysfunction ◽  
Male Rats ◽  
Inhibitory Influence ◽  
Partial Bladder Outlet Obstruction ◽  
Final Stress

Barrington's nucleus, in the pons, regulates micturition through spinal projections to preganglionic parasympathetic neurons. The stress neuropeptide CRF is prominent in these projections and has an inhibitory influence. Social stress in rats causes urinary retention and abnormal urodynamics resembling those produced by partial bladder outlet obstruction (pBOO), and this is associated with CRF upregulation in Barrington's nucleus. Here, we examined the role of CRF in social stress- and pBOO-induced urodynamic dysfunction by assessing the ability of a CRF1 receptor antagonist to alter these effects. Male rats exposed to repeated resident-intruder stress were administered vehicle or a CRF1 antagonist (NBI-30775) daily prior to the stress. Urodynamic function was recorded in the unanesthetized state 72 h after the final stress. NBI-30775 prevented the increased intermicturition interval, micturition volume, and bladder capacity produced by social stress, but not the increase in CRF expression in Barrington's nucleus neurons. The urinary dysfunction was also partly prevented by shRNA targeting of CRF in Barrington's nucleus, suggesting that stress-induced urinary dysfunction results, in part, from CRF upregulation in Barrington's nucleus and enhanced postsynaptic effects in the spinal cord. Finally, NBI-30775 improved urodynamic function of rats that had pBOO of 2-wk duration when administered daily during the second week but did not block the increase in CRF expression in Barrington's nucleus neurons. These findings implicate a role for Barrington's nucleus CRF in stress- and pBOO-induced urodynamic changes and suggest that CRF1 antagonists may be useful therapeutic agents for the treatment of urinary dysfunction.

Regulation of catecholamine-synthesizing enzymes in adrenals of Wistar rats under chronic stress

1993 ◽  
Vol 264 (5) ◽  
pp. R957-R962 ◽  
Author(s):  
V. Lemaire ◽  
M. Le Moal ◽  
P. Mormede
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Social Stress ◽  
Specific Activity ◽  
Sympathetic Innervation ◽  
Male Rats ◽  
Adrenal Weight ◽  
Inhibitory Influence ◽  
Chronic Social Stress ◽  
Sympathetic Nervous

We have shown previously that chronic social stress has differential effects on adrenal weight and on tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) specific activity, depending on the experimental design. To determine the role of the sympathetic nervous system and of the hypothalamo-pituitary-adrenocortical axis (HPAA) in these modifications, we studied the mechanisms of regulation of these parameters in basal conditions as well as in response to reserpine treatment and chronic social stress in the Wistar strain of rats. We found that the adrenal weight is mostly dependent on the activity of the HPAA, which is increased in male rats living in mixed-sex colonies. PNMT specific activity is regulated by splanchnic innervation, confirming that its induction by social instability is a consequence of sympathetic nervous system hyperactivity. The increase of TH specific activity, as seen in unstable, mixed-sex colonies, is not under sympathetic control. However, we show that the pituitary may exert a tonic inhibitory influence, dependent on the sympathetic innervation. These data confirm that the HPAA and the sympathetic nervous system may be independently triggered in chronic social stress conditions.

scholarly journals Role of CRF receptor 1 antagonism in the bed nucleus of the stria terminalis of male rats after intermittent social defeat stress

2019 ◽  
Author(s):  
Mailton Vasconcelos ◽  
Dirson J. Stein ◽  
Matheus Gallas-Lopes ◽  
Luane Landau ◽  
Luiza Behrens ◽  
...  
Keyword(s):  
Social Behavior ◽  
Social Stress ◽  
Social Behaviors ◽  
Social Defeat ◽  
Corticotropin Releasing Factor ◽  
Male Rats ◽  
Stria Terminalis ◽  
Social Avoidance ◽  
Bed Nucleus ◽  
Sweet Solution

AbstractWe recently demonstrated that the experience of brief episodes of social defeat caused impairments in social behaviors. Moreover, we provided evidence that the antagonism of corticotropin-releasing factor binding protein (CRFBP) in the bed nucleus of the stria terminalis (BNST) restored social approach in stressed animals. This study aimed to test the relation between corticotropin-releasing factor receptor type 1 (CRFR1) located in the BNST and the establishment of social stress-disrupted behaviors in rats submitted to social defeat in the resident-intruder paradigm. Animals were tested for sweet solution preference, subjected to the elevated-plus maze (EPM), and to the social interaction three-chamber test. Social behavior was tested after BNST drug infusions. The drug used in this study was a CRF receptor 1 antagonist, CP376395 (CP), administered in two doses: 50 ng/0.20 μL/side, and 500 ng/0.20 μL/side. Saline solution was used as vehicle and administered 0.20 μL/side. Socially stressed animals (n = 11) did not differ compared to control animals (n = 11) in the EPM. Stressed animals displayed impaired social behavior, represented by a decrease in time spent in the interaction zone. The lower dose (CP 50 ng/0.20 μL/side) administered intra-BNST restored social behaviors in stressed animals. On the other hand, the higher dose of the CRFR1 antagonist (CP 500 ng/0.20 μL/side) induced social avoidance in rats without a history of agonistic confrontations. These findings implicate BNST CRFR1 signaling in the modulation of social behaviors in rats given the choice to explore an unfamiliar conspecific.

scholarly journals Social stress induces changes in urinary bladder function, bladder NGF content, and generalized bladder inflammation in mice

2014 ◽  
Vol 307 (7) ◽  
pp. R893-R900 ◽  
Author(s):  
Gerald C. Mingin ◽  
Abbey Peterson ◽  
Cuixia Shi Erickson ◽  
Mark T. Nelson ◽  
Margaret A. Vizzard
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Urinary Bladder ◽  
Protein Expression ◽  
Social Stress ◽  
Bladder Dysfunction ◽  
Bladder Capacity ◽  
Bladder Function ◽  
Nerve Growth ◽  
Urinary Bladder Dysfunction

Social stress may play a role in urinary bladder dysfunction in humans, but the underlying mechanisms are unknown. In the present study, we explored changes in bladder function caused by social stress using mouse models of stress and increasing stress. In the stress paradigm, individual submissive FVB mice were exposed to C57BL/6 aggressor mice directly/indirectly for 1 h/day for 2 or 4 wk. Increased stress was induced by continuous, direct/indirect exposure of FVB mice to aggressor mice for 2 wk. Stressed FVB mice exhibited nonvoiding bladder contractions and a decrease in both micturition interval (increased voiding frequency) and bladder capacity compared with control animals. ELISAs demonstrated a significant increase in histamine protein expression with no change in nerve growth factor protein expression in the urinary bladder compared with controls. Unlike stressed mice, mice exposed to an increased stress paradigm exhibited increased bladder capacities and intermicturition intervals (decreased voiding frequency). Both histamine and nerve growth factor protein expression were significantly increased with increased stress compared with control bladders. The change in bladder function from increased voiding frequency to decreased voiding frequency with increased stress intensity suggests that changes in social stress-induced urinary bladder dysfunction are context and duration dependent. In addition, changes in the bladder inflammatory milieu with social stress may be important contributors to changes in urinary bladder function.

scholarly journals 2429 Optogenetic stimulation of corticotropin-releasing hormone expressing neurons in Barrington’s nucleus recapitulates the social stress voiding phenotype in mice

2018 ◽  
Vol 2 (S1) ◽  
pp. 23-23
Author(s):  
Jason Van Batavia ◽  
Stephan Butler ◽  
Joanna Fesi ◽  
Rita Valentino ◽  
Stephen Zderic
Keyword(s):  
Social Stress ◽  
Bladder Capacity ◽  
Significant Rise ◽  
Corticotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Optogenetic Stimulation ◽  
Void Volumes ◽  
Voiding Postponement ◽  
Stimulation Of

OBJECTIVES/SPECIFIC AIMS: Voiding postponement is common cause of LUT dysfunction in which children void infrequently with large volumes. This condition is modeled in mice that are subjected to social stress who show decreased voiding frequency and increased voided volumes along with increases in corticotropin-releasing hormone (CRH) expression in Barrington’s nucleus (BN) (i.e., the pontine micturition center). Optogenetics is a technique to selectively stimulate cells or neurons of interest via light activated channel receptors [i.e., channel-2 rhodopsin (ChR2)]. Here we examined the effects of optogenetic manipulation of CRH BN neurons on the in vivo voiding phenotype and urodynamics in awake mice. We hypothesized that stimulating these neurons at higher frequencies (10–50 Hz) would lead to CRH-dependent alterations in voiding phenotype (i.e., larger voided volumes and longer intermicturition intervals. METHODS/STUDY POPULATION: Double transgenic mice expressing ChR2 in CRH cells were generated using the Cre-lox recombinase system and had fiberoptic probes implanted into BN at 8 weeks of age. The mice also underwent simultaneous catheter placement into the bladder for in vivo cystometry. In vivo cystometry before and during optogenetic stimulation at various frequencies was performed 5–7 days postoperatively. Saline was perfused at 10 µL/minute and baseline stable voiding cycles were established. Bladder capacity, threshold pressure, voiding pressure, and voided volume were recorded at baseline and at each optogenetic setting. In some mice, the protocol was repeated in the presence of CRH antagonist (NBI 30775). RESULTS/ANTICIPATED RESULTS: Fiberoptic stimulation (470 nm at 25 and 50 Hz) produced a significant rise in the intermicturition interval, bladder capacities and increased void volumes. This effect was especially pronounced in females in whom bladder capacity and intermicturition interval more than doubled at 50 Hz stimulation. Fluoroscopic images confirmed complete bladder emptying with each void. The increased bladder capacity at higher frequencies (25 and 50 Hz) was CRH-dependent as injection of a CRH antagonist (NBI 30775) blocked the optogenetic effect. Control non-double mice showed no effects from optogenetic stimulation. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results suggest that optogenetic stimulation of CRH-expressing neurons in BN at high frequency (25 and 50 Hz) inhibits micturition and recapitulates the voiding phenotype seen in socially stressed mice (large, infrequent voids). Lower frequencies of optogenetic stimulation (2 and 10 Hz) had no effects on cystometry parameters or voiding phenotype. In addition, females had a greater response to optogenetic stimulation compared with males with larger bladder capacities and longer intermicturition intervals. The changes in voiding phenotype seen were CRH dependent as blockage of the CRH receptor prevented changes in cystometry parameters with optogenetic stimulation. Further elucidation of these and other neural subpopulations in BN are warranted to understand micturition and how it may be manipulated in disease states such as voiding postponement and acute urinary retention.

scholarly journals Intravesical TRPV4 blockade reduces repeated variate stress-induced bladder dysfunction by increasing bladder capacity and decreasing voiding frequency in male rats

2014 ◽  
Vol 307 (4) ◽  
pp. R471-R480 ◽  
Author(s):  
Liana Merrill ◽  
Margaret A. Vizzard
Keyword(s):  
Smooth Muscle ◽  
Transient Receptor Potential ◽  
Bladder Dysfunction ◽  
Bladder Capacity ◽  
Bladder Pain Syndrome ◽  
Male Rats ◽  
Bladder Function ◽  
Detrusor Smooth Muscle ◽  
Bladder Pain

Individuals with functional lower urinary tract disorders including interstitial cystitis (IC)/bladder pain syndrome (BPS) and overactive bladder (OAB) often report symptom (e.g., urinary frequency) worsening due to stress. One member of the transient receptor potential ion channel vanilloid family, TRPV4, has recently been implicated in urinary bladder dysfunction disorders including OAB and IC/BPS. These studies address the role of TRPV4 in stress-induced bladder dysfunction using an animal model of stress in male rats. To induce stress, rats were exposed to 7 days of repeated variate stress (RVS). Quantitative PCR data demonstrated significant ( P ≤ 0.01) increases in TRPV4 transcript levels in urothelium but not detrusor smooth muscle. Western blot analyses of split urinary bladders (i.e., urothelium and detrusor) showed significant ( P ≤ 0.01) increases in TRPV4 protein expression levels in urothelial tissues but not detrusor smooth muscle. We previously showed that RVS produces bladder dysfunction characterized by decreased bladder capacity and increased voiding frequency. The functional role of TRPV4 in RVS-induced bladder dysfunction was evaluated using continuous, open outlet intravesical infusion of saline in conjunction with administration of a TRPV4 agonist, GSK1016790A (3 μM), a TRPV4 antagonist, HC067047 (1 μM), or vehicle (0.1% DMSO in saline) in control and RVS-treated rats. Bladder capacity, void volume, and intercontraction interval significantly decreased following intravesical instillation of GSK1016790A in control rats and significantly ( P ≤ 0.01) increased following administration of HC067047 in RVS-treated rats. These results demonstrate increased TRPV4 expression in the urothelium following RVS and that TRPV4 blockade ameliorates RVS-induced bladder dysfunction consistent with the role of TRPV4 as a promising target for bladder function disorders.

Neurogenic bladder in parkinsonism: effect of thalamotomy

1971 ◽  
Vol 34 (1) ◽  
pp. 27-32 ◽  
Author(s):  
Robert W. Porter ◽  
Ernest Bors
Keyword(s):  
Urinary Retention ◽  
Neurogenic Bladder ◽  
Surgical Therapy ◽  
Acute Urinary Retention ◽  
Bladder Dysfunction ◽  
Bladder Capacity ◽  
Pressure Response ◽  
Content Type ◽  
Detrusor Function ◽  
Fine Print

✓ In a group of 62 patients with Parkinsonism, 44 had significant bladder dysfunction, although only one had acute urinary retention. Twenty-five showed a hyperactive type of detrusor function with decreased capacity and an increased volume/pressure response on cystometrography. Of these 25 patients, 23 had marked somatic rigidity with or without tremor. In contrast, 19 patients had hypoactive function manifested by an increased bladder capacity and a decreased volume/pressure response shown in the cystometrogram; of this group 11 had marked tremor with very little rigidity. Forty-nine patients underwent one or more stereotaxic thalamotomies. The effect of surgical therapy on both types of bladder dysfunction was generally favorable in 40 of these patients whose somatic manifestations were satisfactorily controlled.

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