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肌萎缩侧索硬化症小鼠模型下尿路功能障碍的特征分析

Characterization of lower urinary tract dysfunction in a mouse model of amyotrophic lateral sclerosis.

作者信息

Lin Ching-Yi, Nelson Alex, Lee Wayne, Feng Ziqing, Lee Yu-Shang

机构信息

Department of Neurosciences, Cleveland Clinic Research , Cleveland Clinic, Cleveland, OH, 44195, USA.

Cleveland Clinic Lerner College of Medicine of Case Western Reserve University School of Medicine, Cleveland, OH, 44195, USA.

出版信息

Sci Rep. 2025 Aug 9;15(1):29190. doi: 10.1038/s41598-025-15318-9.


DOI:10.1038/s41598-025-15318-9
PMID:40783639
Abstract

Amyotrophic lateral sclerosis (ALS) is characterized by a progressive loss of motor function due to degeneration of motor neurons. In addition to motor-related symptoms, increasing evidence from clinical studies indicate lower urinary tract (LUT) dysfunctions (urge incontinence) are found in patients with ALS, which causes a significant negative impact on quality of life. However, it remains unclear whether LUT dysfunction can be validated in preclinical ALS models. Here, we attempt to answer this question by using comprehensive urodynamic testing with electromyogram of external urethral sphincter (EUS) activity in both female and male SOD1-G93A ALS mice at both 9 weeks of age (pre-onset stage) and 16 weeks of age (early symptomatic stage). Our results demonstrate that the detrusor muscle is hyperactive, voiding volume is decreased, and the EUS relaxation period is shorter in female and male SOD1-G93A ALS mice at both 9 weeks and 16 weeks of age, compared to age-matched wild-type animals. The symptoms of urge incontinence found in the current study are similar to the clinical findings, indicating that SOD1-G93A ALS mice can be used as a preclinical model to develop therapeutics for ALS patients with LUT dysfunction.

摘要

肌萎缩侧索硬化症(ALS)的特征是由于运动神经元变性导致运动功能逐渐丧失。除了与运动相关的症状外,临床研究越来越多的证据表明,ALS患者存在下尿路(LUT)功能障碍(急迫性尿失禁),这对生活质量产生了重大负面影响。然而,尚不清楚LUT功能障碍是否能在临床前ALS模型中得到验证。在此,我们试图通过对9周龄(发病前期)和16周龄(早期症状期)的雌性和雄性SOD1-G93A ALS小鼠进行综合尿动力学测试,并记录尿道外括约肌(EUS)活动的肌电图,来回答这个问题。我们的结果表明,与年龄匹配的野生型动物相比,9周龄和16周龄的雌性和雄性SOD1-G93A ALS小鼠的逼尿肌活动亢进、排尿量减少且EUS松弛期缩短。本研究中发现的急迫性尿失禁症状与临床发现相似,表明SOD1-G93A ALS小鼠可作为临床前模型,用于开发针对患有LUT功能障碍的ALS患者的治疗方法。

相似文献

[1]
Characterization of lower urinary tract dysfunction in a mouse model of amyotrophic lateral sclerosis.

Sci Rep. 2025-8-9

[2]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[10]
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本文引用的文献

[1]
Lower urinary tract dysfunction following stroke: From molecular mechanisms to clinical anatomy.

J Biol Methods. 2024-9-13

[2]
Long-Term 5-HT Receptor Agonist NLX-112 Treatment Improves Functional Recovery After Spinal Cord Injury.

Int J Mol Sci. 2024-12-30

[3]
Non-motor symptoms in patients with amyotrophic lateral sclerosis: current state and future directions.

J Neurol. 2024-7

[4]
Skin innervation across amyotrophic lateral sclerosis clinical stages: new prognostic biomarkers.

Brain. 2024-5-3

[5]
Dysautonomia in Amyotrophic Lateral Sclerosis.

Int J Mol Sci. 2023-10-5

[6]
Autonomic dysfunction is associated with disease progression and survival in amyotrophic lateral sclerosis: a prospective longitudinal cohort study.

J Neurol. 2023-10

[7]
Upregulated 5-HT Receptors Regulate Lower Urinary Tract Function in Rats after Complete Spinal Cord Injury.

J Neurotrauma. 2023-5

[8]
Amyotrophic lateral sclerosis: a neurodegenerative disorder poised for successful therapeutic translation.

Nat Rev Drug Discov. 2023-3

[9]
Current Knowledge and Novel Frontiers in Lower Urinary Tract Dysfunction after Spinal Cord Injury: Basic Research Perspectives.

Urol Sci. 2022

[10]
Prevalence of lower urinary tract symptoms, urinary incontinence and retention in Parkinson's disease: A systematic review and meta-analysis.

Front Aging Neurosci. 2022-9-12

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