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

Sakakibara, Ryuji; Hattori, Takamichi; Uchiyama, Tomoyuki; Sasajima, Tadahiro; Takahashi, Hirokazu; Yamanishi, Tomonori; Egoshi, Ken-ichi; Sekita, Nobuyuki

doi:10.1016/s0165-1838(99)00105-8

Cited by 61 publications

(31 citation statements)

References 16 publications

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“…Since we measured a partial rescue of the symptoms of neurodegeneration in the transgenic mouse with shortterm terazosin treatment (Zuscik et al 2000), we hypothesized that long-term administration of the same drug would be protective of the disease. In fact, a human pilot study has already shown that a 1 -AR blockers improved lower urinary tract dysfunction commonly seen in MSA patients (Sakakibara et al 2000). This could offer potential therapeutic possibilities to people who have known genetic mutations (synucleinopathies) that result in parkinsonian-like diseases, if a 1 -AR stimulation can contribute to the pathology.…”

Section: Discussionmentioning

confidence: 94%

Mice expressing the α_1B‐adrenergic receptor induces a synucleinopathy with excessive tyrosine nitration but decreased phosphorylation

Papay

Zuscik

Ross

et al. 2002

Journal of Neurochemistry

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We had previously reported that systemic overexpression of the a 1B -adrenergic receptor (AR) in a transgenic mouse induced a neurodegenerative disease that resembled the parkinsonian-like syndrome called multiple system atrophy (MSA). We now report that our mouse model has cytoplasmic inclusion bodies that colocalize with oligodendrocytes and neurons, are positive for a-synuclein and ubiquitin, and therefore may be classified as a synucleinopathy. a-Synuclein monomers as well as multimers were present in brain extracts from both normal and transgenic mice. However, similar to human MSA and other synucleinopathies, transgenic mice showed an increase in abnormal aggregated forms of a-synuclein, which also increased its nitrated content with age.However, the same extracts displayed decreased phosphorylation of a-synuclein. Other traits particular to MSA such as Purkinje cell loss in the cerebellum and degeneration of the intermediolateral cell columns of the spinal cord also exist in our mouse model but differences still exist between them. Interestingly, long-term therapy with the a 1 -AR antagonist, terazosin, resulted in protection against the symptomatic as well as the neurodegeneration and a-synuclein inclusion body formation, suggesting that signaling of the a 1B -AR is the cause of the pathology. We conclude that overexpression of the a 1B -AR can cause a synucleinopathy similar to other parkinsonian syndromes.

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Section: Discussionmentioning

confidence: 94%

Mice expressing the α_1B‐adrenergic receptor induces a synucleinopathy with excessive tyrosine nitration but decreased phosphorylation

Papay

Zuscik

Ross

et al. 2002

Journal of Neurochemistry

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“…17 ␣-Adrenergic receptor antagonists (prazosin and moxisylyte) have been shown to improve voiding with reduction of residual volumes in MSA patients. 64 Urological surgery must be avoided in these patients because postoperative worsening of bladder control is most likely. 17 The necessity of a specific treatment for sexual dysfunction needs to be evaluated individually in each MSA patient.…”

Section: S38 Gk Wenning Et Almentioning

confidence: 99%

Multiple system atrophy: An update

et al. 2003

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Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder that usually manifests in the early sixth decade of life and progresses relentlessly with a mean survival of 9 years. Clinically, MSA is dominated by autonomic/urogenital failure, which may be associated with either levodopa (L-dopa) -unresponsive parkinsonism in 80% of cases (MSA-P subtype) or with cerebellar ataxia in 20% of cases (MSA-C subtype). Pathologically, MSA is characterized by a neuronal multisystem degeneration and abnormal glial cytoplasmic inclusions containing alpha-synuclein aggregates. Pharmacological treatment of motor features is disappointing except for a transient L-dopa response in a minority of MSA-P patients. In contrast, autonomic and urogenital features of MSA should be identified early on, because they can be treated effectively in many instances. Neuroprotective strategies are presently unavailable, however, two multicentre European trials have been launched to evaluate the effects of riluzole and human recombinant growth hormone on disease progression in MSA. Clearly, further randomised, controlled trials are required to identify effective symptomatic or neuroprotective agents in MSA. Several in vivo models have become available to allow a careful preselection of candidate agents. Several research groups have been formed in Europe (EMSA-SG, NNIPPS) and United States (NAMSA-SG), providing a framework for coordinated trial activity in MSA.

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“…Therefore, we prescribed tamsulosin, an a-adrenergic blocking agent [Michel et al, 1998], which ameliorated his urinary frequency and voiding dif®culty. An approach for the treatment of urinary dysfunction in BS patients may require a combination of therapies for the underlying disorders with a-adrenergic blocking agents [Michel et al, 1998;Sakakibara et al, 2000] and clean, intermittent self-catheterization for large residuals.…”

Section: Discussionmentioning

confidence: 99%

“…None of the men had apparent prostatic hypertrophy by digital examination or ultrasound echography. The methods and de®nitions used for the urodynamic studies were described in detail previously [Sakakibara et al, 2000] and conformed to the standards proposed by the International Continence Society [Abrams et al, 1989].…”

Section: Methodsmentioning

confidence: 99%

Urinary dysfunction in Brown‐Séquard syndrome

Sakakibara

Hattori

Uchiyama

et al. 2001

Neurourology and Urodynamics

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Brown-Séquard syndrome (BS) is a rare but well documented condition of the spinal cord hemisection, comprising hemiparesis with crossed superficial sensory disturbance. However, little is known of micturitional function in BS, although some patients with BS are troubled with severe voiding difficulty and urinary incontinence. We performed urinary questionnaire and urodynamic studies in eight patients with BS, including seven men and one woman, mean age of 41 years. Detailed questionnaire showed that five of the eight patients (63%) had micturitional symptoms, including voiding difficulty in three, urinary retention in two, urinary frequency in two and urge urinary incontinence in one. Urodynamic abnormalities were noted in all five patients with micturitional symptoms, including post-micturition residuals in four (average 149 mL), high urethral closure pressure in two, increased bladder volume at first sensation in one, detrusor hyperreflexia in four, detrusor areflexia on voiding in three and unrelaxing sphincter on voiding in four. Three asymptomatic patients showed normal urodynamic finding. Micturitional symptoms were more common in patients with severe motor paresis (100%) than in those with mild motor paresis (40%), and there was no relation between micturitional disturbance with superficial or deep sensory disturbance. A combination of treatments for the underlying disorders with alpha-adrenergic blocking agent and clean, intermittent self-catheterization ameliorated the urinary dysfunction in all patients together with neurological dysfunction. In conclusion, micturitional disturbance was not uncommon in our patients with BS, particularly in those with severe motor paresis, which could ameliorate by appropriate therapies.

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

Cited by 61 publications

References 16 publications

Mice expressing the α_1B‐adrenergic receptor induces a synucleinopathy with excessive tyrosine nitration but decreased phosphorylation

Mice expressing the α_1B‐adrenergic receptor induces a synucleinopathy with excessive tyrosine nitration but decreased phosphorylation

Multiple system atrophy: An update

Urinary dysfunction in Brown‐Séquard syndrome

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

Cited by 61 publications

References 16 publications

Mice expressing the α1B‐adrenergic receptor induces a synucleinopathy with excessive tyrosine nitration but decreased phosphorylation

Mice expressing the α1B‐adrenergic receptor induces a synucleinopathy with excessive tyrosine nitration but decreased phosphorylation

Multiple system atrophy: An update

Urinary dysfunction in Brown‐Séquard syndrome

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Product

Resources

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Mice expressing the α_1B‐adrenergic receptor induces a synucleinopathy with excessive tyrosine nitration but decreased phosphorylation

Mice expressing the α_1B‐adrenergic receptor induces a synucleinopathy with excessive tyrosine nitration but decreased phosphorylation