外周神经的光遗传学控制：体内逼尿肌收缩调节的新方法。

IF 2.3 4区医学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of Neuroscience Methods Pub Date : 2025-09-26 DOI:10.1016/j.jneumeth.2025.110591

Akihiro Maeda , Fumiaki Yoshida , Maki Kawasaki , Shohei Tobu , Hiroaki Kakinoki , Hiroki Yasuda , Mitsuru Noguchi

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引用次数: 0

摘要

背景：下尿路症状（LUTS），特别是排尿功能障碍的患病率日益增加，已成为老龄化社会中一个值得关注的问题。传统的治疗方法，包括药物治疗和骶骨神经调节，疗效有限或涉及侵入性手术。迫切需要新颖、精确、微创的神经调节技术来恢复膀胱收缩力而不影响尿失禁。新方法：我们开发了一种体内光遗传学方法，通过将一种编码光敏离子通道的腺相关病毒（aav9 - hsync - soul）直接递送到Sprague-Dawley大鼠的膀胱壁来调节膀胱逼尿肌活性。注射后4周，进行膀胱测量以评估膀胱对蓝光（473nm）刺激的反应。组织学分析证实了转基因在周围神经中的表达。结果：经膀胱计量分析证实，光刺激显著增加了所有注射载体大鼠的膀胱压力。刺激后尿间隔和排尿量无明显变化。免疫荧光染色显示SOUL表达与外周神经标记物外周素在膀胱壁共定位。与现有方法的比较：与电刺激和药物相比，这种光遗传学方法提供了靶向和可逆的膀胱收缩控制，而不需要转基因动物模型或全身暴露。它为骶骨神经调节提供了一种侵入性较小的替代方法，并提高了特异性。结论：本研究表明，利用aav介导的SOUL表达光基因刺激膀胱周围神经可有效增强逼尿肌收缩力，同时保持排尿功能。这些发现支持光控、微创神经调节策略治疗排尿功能障碍的可行性。

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Optogenetic control of peripheral nerves: A novel approach to modulation of detrusor contractility in vivo

Background

The increasing prevalence of lower urinary tract symptoms (LUTS), particularly voiding dysfunction, has become a significant concern in aging societies. Conventional treatments, including pharmacotherapy and sacral neuromodulation, offer limited efficacy or involve invasive procedures. There is a pressing need for novel, precise, and minimally invasive neuromodulation techniques to restore bladder contractility without compromising continence.

New method

We developed an in vivo optogenetic approach to modulate bladder detrusor activity by delivering an adeno-associated virus (AAV9-hSyn-SOUL) encoding a light-sensitive ion channel directly into the bladder wall of Sprague-Dawley rats. Four weeks post-injection, cystometry was conducted to evaluate bladder responses to blue light (473 nm) stimulation. Histological analysis confirmed transgene expression in peripheral nerves.

Results

Optical stimulation significantly increased intravesical pressure in all vector-injected rats, as confirmed by cystometric analysis. Urinary interval and voided volume showed no significant change following stimulation. Immunofluorescence staining revealed co-localization of SOUL expression with the peripheral nerve marker peripherin in the bladder wall.

Comparison with existing methods

Compared to electrical stimulation and pharmacologic agents, this optogenetic approach provided targeted and reversible control of bladder contractions without requiring transgenic animal models or systemic exposure. It offers a less invasive alternative to sacral neuromodulation with improved specificity.

Conclusions

This study demonstrates that optogenetic stimulation of the peripheral bladder nerves using AAV-mediated SOUL expression effectively enhances detrusor contractility while preserving voiding function. These findings support the feasibility of a light-controlled, minimally invasive neuromodulation strategy for the treatment of voiding dysfunction.

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来源期刊

Journal of Neuroscience Methods 医学-神经科学

CiteScore

7.10

自引率

3.30%

发文量

226

审稿时长

52 days

期刊介绍： The Journal of Neuroscience Methods publishes papers that describe new methods that are specifically for neuroscience research conducted in invertebrates, vertebrates or in man. Major methodological improvements or important refinements of established neuroscience methods are also considered for publication. The Journal''s Scope includes all aspects of contemporary neuroscience research, including anatomical, behavioural, biochemical, cellular, computational, molecular, invasive and non-invasive imaging, optogenetic, and physiological research investigations.