Alteration in brain activation sites in response to bladder filling may be related to the pathophysiology of detrusor overactivity in patients with Parkinson's disease.

Although patients with hypospadias had a slightly higher rate of dissatisfaction with penile size, their sexual behavior was not different from that in control subjects.

Miyazato M, Kaiho Y, Kamo I, Kitta T, Chancellor MB, Sugaya K, Arai Y, de Groat WC, Yoshimura N. Role of spinal serotonergic pathways in sneeze-induced urethral continence reflex in rats. Am J Physiol Renal Physiol 297: F1024 -F1031, 2009. First published July 29, 2009 doi:10.1152/ajprenal.00297.2009.-To clarify the role of spinal serotonergic mechanisms in preventing stress urinary incontinence (SUI) during sneezing, we investigated the effect of intrathecal (it) application of 8-OH-DPAT (a 5-HT1A agonist), mCPP (a 5-HT2B/2C agonist), and fluoxetine (a serotonin reuptake inhibitor) using a rat model that can examine the neurally evoked continence reflex during sneezing. Amplitudes of urethral pressure responses during sneezing (A-URS), urethral baseline pressure (UBP) at the midurethra, and sneeze-induced leak point pressure (S-LPP) were measured in normal female adult rats and rats with SUI induced by vaginal distention (VD). In normal rats, 8-OH-DPAT decreased A-URS by 48.9%, whereas mCPP increased A-URS by 33.6%. However, A-URS was not changed after fluoxetine. 8-OH-DPAT, mCPP, or fluoxetine did not alter UBP. The effect of 8-OH-DPAT and mCPP was antagonized by WAY-100635 (it), a selective 5-HT1A antagonist, and RS-102221 (it), a selective 5-HT2C antagonist, respectively. Fluoxetine in the presence of WAY-100635 did not change either A-URS or UBP, but fluoxetine in the presence of RS-102221 decreased A-URS. In VD rats, S-LPP was decreased by 14.6 cmH2O after 8-OH-DPAT, whereas it was increased by 12.8 cmH2O after mCPP. However, S-LPP was not changed after fluoxetine. These results indicate that activation of 5-HT2C receptors enhances the active urethral closure reflex during sneezing at the spinal level, whereas 5-HT1A inhibits it and that no apparent changes in the sneeze-induced continence reflex after fluoxetine treatment are due to coactivation of excitatory 5-HT2C receptors and inhibitory 5-HT receptors other than the 5-HT1A subtype. Thus, activation of excitatory 5-HT receptor subtypes such as 5-HT2C could be effective for the treatment of SUI. urinary incontinence; neural pathway; serotonergic reuptake inhibitors; birth trauma STRESS URINARY INCONTINENCE (SUI) is the most common type of urinary incontinence in women after middle age. Urethral hypermobility and intrinsic sphincter deficiency are two main conditions found in patients with SUI (17). The mechanisms that maintain urinary continence during elevation of abdominal pressure include both passive and active closures of the urethra (5). We previously established a rat model that can be used to examine sneeze-induced active urethral closure mechanisms that are mediated by somatic nerve-induced reflex contractions of external urethral sphincter and pelvic floor striated muscles (14). Our previous study also showed that these active urethral closure mechanisms during sneezing are impaired in a rat model of SUI induced by simulated birth trauma (15).Onuf's nucleus in the sacral cord, which sends somatic input to external urethral sphincter and pelvi...

A review of functional brain imaging studies of bladder control in participants with normal control and pathological conditions. In the normal condition, bladder and urethral afferents received in the periaqueductal gray relay the information to the insula, the anterior cingulate cortex and the prefrontal cortex. During the storage phase, these superior regions control the pontine micturition center to inhibit voiding. In overactive bladder patients, brain responses are different. Cortical responses become exaggerated, especially in the anterior cingulate cortex and the supplementary motor area. That is what presumably evokes the "urgency". The supplementary motor area is activated during contraction of the pelvic floor muscles, and provides protection against incontinence. We believe that functional brain imaging studies are promising not only for the understanding of bladder dysfunction, but also as an aid to the development of therapeutic options for chronic disorders.

The lower urinary tract is controlled by complex neural mechanisms not only in the periphery, but also in the central nervous systems (CNS). Thus, patients with a wide variety of neurological diseases often also have lower urinary tract symptoms (LUTS), including those with Parkinson disease (PD) or multiple system atrophy (MSA). LUTS are common comorbidities associated with both of these neurodegenerative diseases and are likely to impair patients' quality of life. The motor symptoms of PD and MSA often seem similar; however, the pathophysiology, and thus the treatment of LUTS differs considerably. Antimuscarinics are the first-line treatment of storage LUTS in patients with PD or MSA; however, care should be taken in the management of these patients, especially in those with MSA owing to the high risk of inefficient voiding, and thus an increased post-void residual volume. Other treatments of PD-related LUTS include α-adrenoceptor antagonists, which improve voiding dysfunction, transurethral resection of the prostate for bladder outlet obstruction owing to prostate enlargement, and neuromodulation and intradetrusor botulinum toxin injections for storage LUTS. However, more conservative treatments, including intermittent catheterization, are required for LUTS in patients with MSA, owing to the high incidence of impaired detrusor contractility and detrusor-sphincter dyssynergia.

The periaqueductal gray (PAG) is critically involved in the micturition reflex, but little is known about the neuronal mechanisms involved. The present study elucidated dynamic changes in dopamine (DA), glutamate and gamma-aminobutyric acid (GABA) in the rat PAG during the micturition reflex, with a focus on dopaminergic modulation using in vivo microdialysis combined with cystometrography. Extracellular levels of DA and glutamate increased, whereas levels of GABA decreased, in parallel with the micturition reflex. Application of a D(1) receptor antagonist into the PAG produced increases in maximal voiding pressure (MVP) and decreases in intercontraction interval (ICI), suggesting that the micturition reflex was facilitated by D(1) receptor blockade. The D(1) receptor antagonist prevented micturition-induced decreases in GABA efflux but had no effect on DA or glutamate. Neither a D(2) receptor antagonist nor a D(1)/D(2) receptor agonist affected these neurochemical and physiological parameters. Micturition-induced inhibition of GABA was not observed in 6-hydroxydopamine (6-OHDA)-lesioned rats, an animal model of Parkinson's disease. 6-OHDA-lesioned rats exhibited bladder hyperactivity evaluated by increases in MVP and decreases in ICI, mimicking facilitation of the micturition reflex induced by D(1) receptor blockade. These findings suggest that the micturition reflex is under tonic dopaminergic regulation through D(1) receptors, in which a GABAergic mechanism is involved. Bladder hyperactivity observed in 6-OHDA-lesioned rats may be caused by dysfunction of GABAergic regulation underlying the micturition reflex. The present findings contribute to our understanding not only of the neurophysiology of the micturition reflex but also of the pathophysiology of lower urinary tract dysfunction in patients with Parkinson's disease.

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Prenatal sex hormones can induce abnormalities in the reproductive system and adversely impact on genital development. We investigated whether sex hormones in cord blood influenced the ratio of the second to fourth digit lengths (2D/4D) in school-aged children. Of the 514 children who participated in a prospective cohort study on birth in Sapporo between 2002 and 2005, the following sex hormone levels were measured in 294 stored cord blood samples (135 boys and 159 girls); testosterone (T), estradiol (E), progesterone, LH, FSH, inhibin B, and insulin-like factor 3 (INSL3). A total of 350 children, who were of school age and could be contacted for this survey, were then requested via mail to send black-and-white photocopies of the palms of both the left and right hands. 2D/4D was calculated in 190 children (88 boys and 102 girls) using photocopies and derived from participants with the characteristics of older mothers, a higher annual household income, higher educational level, and fewer smokers among family members. 2D/4D was significantly lower in males than in females (p<0.01). In the 294 stored cord blood samples, T, T/E, LH, FSH, Inhibin B, and INSL3 levels were significantly higher in samples collected from males than those from females. A multivariate regression model revealed that 2D/4D negatively correlated with INSL3 in males and was significantly higher in males with <0.32 ng/mL of INSL3 (p<0.01). No correlations were observed between other hormones and 2D/4D. In conclusion, 2D/4D in school-aged children, which was significantly lower in males than in females, was affected by prenatal Leydig cell function.