scholarly journals Spread of pathological α-synuclein from urogenital nerves initiates multiple system atrophy-like symptoms

2019 ◽  
Author(s):  
Xuejing Wang ◽  
Mingming Ma ◽  
Erxi Wu ◽  
Dongyang Teng ◽  
Xin Yuan ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Multiple System Atrophy ◽  
Lower Urinary Tract ◽  
Motor Impairments ◽  
External Urethral Sphincter ◽  
Micturition Reflex ◽  
Reflex Pathways ◽  
Urogenital Dysfunction ◽  
The Brain ◽  
Lower Urinary

AbstractMultiple system atrophy (MSA) is a fatal adult-onset movement disorder with autonomic failures, especially urogenital dysfunction. The neuropathological feature of MSA is the accumulation of misfolded α-synuclein (α-Syn) in the nervous system. Here, we show that misfolded α-Syn exist in nerve terminals in detrusor (DET) and external urethral sphincter (EUS) of patients with MSA. Moreover, α-Syn preformed fibrils inoculated into the EUS or DET in TgM83+/− mice initiated the transmission of misfolded α-Syn from the lower urinary tract to brain, and these mice developed α-Syn inclusion pathology through micturition reflex pathways along with urinary dysfunction and motor impairments. These findings indicate that spreading of misfolded α-Syn from the autonomic control of the lower urinary tract to the brain via micturition reflex pathways induces autonomic failure and motor impairments. These results provide important new insights into the pathogenesis of MSA as well as highlight potential targets for early detection and therapeutics.

scholarly journals Past, Present, and Future in the Study of Neural Control of the Lower Urinary Tract

2020 ◽  
Vol 24 (3) ◽  
pp. 191-199
Author(s):  
Jin Wook Kim ◽  
Su Jin Kim ◽  
Khae Hawn Kim
Keyword(s):  
Urinary Tract ◽  
Motor Neurons ◽  
Lower Urinary Tract ◽  
Neural Control ◽  
Sympathetic Neurons ◽  
Voluntary Contraction ◽  
Sensory Nerves ◽  
External Urethral Sphincter ◽  
Complex Signals ◽  
Lower Urinary

The neurological coordination of the lower urinary tract can be analyzed from the perspective of motor neurons or sensory neurons. First, sensory nerves with receptors in the bladder and urethra transmits stimuli to the cerebral cortex through the periaqueductal gray (PAG) of the midbrain. Upon the recognition of stimuli, the cerebrum carries out decision-making in response. Motor neurons are divided into upper motor neurons (UMNs) and lower motor neurons (LMNs) and UMNs coordinate storage and urination in the brainstem for synergic voiding. In contrast, LMNs, which originate in the spinal cord, cause muscles to contract. These neurons are present in the sacrum, and in particular, a specific neuron group called Onuf’s nucleus is responsible for the contraction of the external urethral sphincter and maintains continence in states of rising vesical pressure through voluntary contraction of the sphincter. Parasympathetic neurons originating from S2–S4 are responsible for the contraction of bladder muscles, while sympathetic neurons are responsible for contraction of the urethral smooth muscle, including the bladder neck, during the guarding reflex. UMNs are controlled in the pons where various motor stimuli to the LMNs are directed along with control to various other pelvic organs, and in the PAG, where complex signals from the brain are received and integrated. Future understanding of the complex mechanisms of micturition requires integrative knowledge from various fields encompassing these distinct disciplines.

Neurogenic dysfunction of the lower urinary tract (neurogenic bladder)

2021 ◽  
Vol 26 (5) ◽  
pp. 61-72
Author(s):  
Yu. N. Sorokin
Keyword(s):  
Urinary Tract ◽  
Neurogenic Bladder ◽  
Lower Urinary Tract ◽  
Neural Control ◽  
Clinical Symptoms ◽  
Neurological Diseases ◽  
Clinical Manifestations ◽  
Neurogenic Dysfunction ◽  
The Brain ◽  
Lower Urinary

The lecture presents information about the central and peripheral structures that provide innervation and regulation of the functions of the lower urinary tract — the bladder and urethra. The mechanisms of regulation of the functions of accumulation and retention of urine (reservoir function) and emptying of the bladder (evacuation function) are shown.Neural control of urination is organized in the form of a hierarchical system. The spinal centers are the executive structures, and the cerebral centers are the controlling structures. Involuntary implementation of the act of urination occurs through segmental sympathetic and parasympathetic mechanisms. The regulation of these functions and voluntary urination are carried out by the central mechanisms of the brain — the actuation of the urination reflex is under strict volitional control, which makes it possible to plan the emptying of the bladder in a socially acceptable place and time.The information on the clinical symptoms of neurogenic dysfunction of the lower urinary tract (neurogenic bladder) is reviewed. The features of clinical manifestations depending on the level of damage to neural structures and in various neurological diseases are shown. Methods for assessing urodynamics and treatment directions for neurogenic dysfunction of the lower urinary tract are presented.

AGE-RELATED CHANGES OF THE FEMALE URETHRA

2021 ◽  
pp. 945-955
Author(s):  
И. В. Майбородин ◽  
Г. Ю. Ярин ◽  
И. А. Вильгельми ◽  
В. И. Майбородина
Keyword(s):  
Urinary Tract ◽  
Lower Urinary Tract ◽  
Striated Muscle ◽  
Relative Length ◽  
External Urethral Sphincter ◽  
Female Urethra ◽  
Smooth Muscle Tissue ◽  
Age Related ◽  
Age Related Changes ◽  
Lower Urinary

Минимальные и максимальные показатели длины, ширины, площади или объема органов и структур нижних мочевых путей в норме могут различаться до 2-3 раз. С возрастом у здоровых женщин не меняются абсолютная и относительная длина мочеиспускательного канала, уретровезикальный угол и наклон уретры. И гладкая, и поперечнополосатая мышечные ткани, входящие в состав различных отделов женской уретры, подвергаются атрофии в процессе старения организма. Гладкая мышечная ткань менее изменчива с возрастом, но поперечнополосатые мышечные симпласты иногда полностью отсутствуют в биоптатах уретры пожилых пациентов. С возрастом уменьшаются васкуляризация и плотность иннервации структур мочеиспускательного канала, но возрастает содержание соединительной ткани в наружном сфинктере уретры. Мобильность мочеиспускательного канала у молодых женщин более выражена, чем у пожилых. Явная недостаточность современных работ, посвященных возрастным изменениям нижних мочевых путей, указывает на актуальность и необходимость продолжения изучения трансформации органов и тканей мочевыводящей системы при старении. Это может быть важным для определения этиологии и патогенеза некоторых патологических состояний, таких как стрессовое недержание мочи, а также для дифференциальной диагностики между возрастной нормой и патологией. The minimum and maximum indicators of the length, width, area or volume of organs and structures in the lower urinary tract can normally vary up to 2-3 times. With age, at healthy women the absolute and relative length of the urethra, the urethrovesical angle, and the inclination of the urethra do not change. Both smooth and striated muscle tissues, which are part of various departments of the female urethra, undergo atrophy during the aging process. Smooth muscle tissue is less variable with age, but striated muscle symplasts are sometimes completely absent in urethral biopsies from elderly patients. With age, the vascularization and density of the innervation decrease in the urethral structures, but the content of connective tissue in the external urethral sphincter increases. Urinary tract mobility at young women is more pronounced than at older women. The apparent insufficiency of modern investigations about age-related changes in the lower urinary tract indicates the relevance and need to continue studying of the organ and tissue transformation in the urinary system during aging, this may be important for determining the etiology and pathogenesis of some pathological conditions, such as stress urinary incontinence, as well as for differential diagnosis between age norm and pathology.

Neural Control of Lower Urinary Tract Function

2019 ◽  
Author(s):  
Jonathan M. Beckel ◽  
William C. de Groat
Keyword(s):  
Nervous System ◽  
Urinary Tract ◽  
Lower Urinary Tract ◽  
Neural Control ◽  
Voluntary Control ◽  
Striated Muscles ◽  
Lumbosacral Spinal Cord ◽  
Lower Urinary Tract Function ◽  
The Brain ◽  
Lower Urinary

Functions of the lower urinary tract to store and periodically eliminate urine are regulated by a complex neural control system in the brain and lumbosacral spinal cord that coordinates the activity of smooth and striated muscles of the bladder and urethral outlet via a combination of voluntary and reflex mechanisms. Many neural circuits controlling the lower urinary tract exhibit switch-like patterns of activity that turn on and off in an all-or-none manner. During urine storage, spinal sympathetic and somatic reflexes are active to maintain a quiescent bladder and a closed outlet. During micturition, these spinal storage reflexes are suppressed by input from the brain, while parasympathetic pathways in the brain are activated to produce a bladder contraction and relaxation of the urethra. The major component of the micturition switching circuit is a spinobulbospinal parasympathetic pathway that consists of essential relay circuitry in the periaqueductal gray and pontine micturition center. These circuits in the rostral brain stem are, in turn, regulated by inputs from the forebrain that mediate voluntary control of micturition. Thus neural control of micturition is organized as a hierarchical system in which spinal storage reflexes and supraspinal voiding reflexes are regulated voluntarily by higher centers in the brain. In young children the voluntary mechanisms are undeveloped and voiding is purely reflex. Voluntary control emerges during maturation of the nervous system and depends on learned behavior. Diseases or injuries of the nervous system in adults cause re-emergence of involuntary micturition, leading to urinary incontinence.

scholarly journals Effects of urethane on reflex activity of lower urinary tract in decerebrate unanesthetized rats

2013 ◽  
Vol 304 (4) ◽  
pp. F390-F396 ◽  
Author(s):  
Mitsuharu Yoshiyama ◽  
James R. Roppolo ◽  
Masayuki Takeda ◽  
William C. de Groat
Keyword(s):  
Urinary Tract ◽  
Lower Urinary Tract ◽  
Nmda Antagonist ◽  
Suppressive Effect ◽  
External Urethral Sphincter ◽  
Mk 801 ◽  
Pressure Threshold ◽  
Lower Urinary Tract Function ◽  
Tract Function ◽  
Lower Urinary

Effects of urethane on lower urinary tract function were examined in decerebrate unanesthetized rats. During single slow infusion (0.04 ml/min) cystometrograms (CMGs), urethane (0.3 g/kg) increased micturition pressure threshold (PT) by 73%, postvoid residual volume (RV) by 425%, and decreased voiding efficiency (VE) by 57%, but did not change maximal voiding pressure (MVP), closing peak pressure (CPP), bladder compliance, bladder contraction duration (BCD), or volume threshold (VT) for inducing micturition. Lower doses (0.01–0.1 g/kg) did not alter any parameter. During continuous fast infusion (0.21 ml/min) CMGs, urethane at doses of 0.6–1.2 g/kg (iv) markedly decreased CPP by 69–85%, whereas only the largest dose (1.2 g/kg iv) decreased MVP and external urethral sphincter electromyogram activity by 42 and by 80%, respectively. Doses of 0.001–0.6 g/kg did not alter the intercontraction interval and BCD. Taken together, these results suggest that urethral activity, which is essential for efficient voiding, is more sensitive to the suppressive effect of urethane than afferent or efferent mechanisms controlling the bladder. The threshold dose of MK-801 (0.3 mg/kg), an NMDA antagonist, required to decrease MVP and increase VT in urethane (1.2 g/kg)-anesthetized rats, only increased VT in rats treated with a subanesthetic dose of urethane (0.3 g/kg), suggesting a higher sensitivity of the afferent vs. efferent limb of the micturition reflex pathway to urethane-MK-801 interactions. Because effects of urethane persisted after removal of the forebrain, they must be mediated by actions on the brain stem, spinal cord, or peripheral nervous system.

scholarly journals High-density spinal cord stimulation selectively activates lower urinary tract afferents

2021 ◽  
Author(s):  
Maria K Jantz ◽  
Chaitanya Gopinath ◽  
Ritesh Kumar ◽  
Celine Chin ◽  
Liane Wong ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Urinary Tract ◽  
Spinal Cord Stimulation ◽  
Lower Urinary Tract ◽  
Cauda Equina ◽  
High Density ◽  
Reflex Pathways ◽  
Epidural Spinal Cord Stimulation ◽  
Urethral Function ◽  
Lower Urinary

Epidural spinal cord stimulation (SCS) has recently been reported as a potential intervention to improve limb and autonomic functions, with lumbar stimulation improving locomotion and thoracic stimulation regulating blood pressure. We asked whether sacral SCS could be used to target the lower urinary tract. Here we show that high-density epidural SCS over the sacral spinal cord and cauda equina of anesthetized cats evokes responses in nerves innervating the bladder and urethra and that these nerves can be activated selectively. Sacral epidural SCS always recruited the pelvic and pudendal nerves and selectively recruited these nerves in all but one animal. Individual branches of the pudendal nerve were always recruited as well. Electrodes that selectively recruited specific peripheral nerves were spatially clustered on the arrays, suggesting anatomically organized sensory pathways. This selective recruitment demonstrates a mechanism to directly modulate bladder and urethral function through known reflex pathways, which could be used to restore bladder and urethral function after injury or disease.

Are alpha-blockers involved in lower urinary tract dysfunction in multiple system atrophy?

2000 ◽  
Vol 79 (2-3) ◽  
pp. 191-195 ◽  
Author(s):  
Ryuji Sakakibara ◽  
Takamichi Hattori ◽  
Tomoyuki Uchiyama ◽  
Tadahiro Suenaga ◽  
Hirokazu Takahashi ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Multiple System Atrophy ◽  
Lower Urinary Tract ◽  
Lower Urinary Tract Dysfunction ◽  
Alpha Blockers ◽  
Lower Urinary
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