Synaptic Vesicle 2A (SV2A) Positron Emission Tomography (PET) Imaging as a Marker of Therapeutic Response in a Mouse Model of Depression.

IF 4.9 Q1 CHEMISTRY, MEDICINAL

ACS Pharmacology and Translational Science Pub Date : 2025-01-28 eCollection Date: 2025-02-14 DOI:10.1021/acsptsci.4c00621

Cassandre Corvo, Indira Mendez-David, Sébastien Goutal, Wadad Saba, Michel Bottlaender, Fabien Caillé, Rene Hen, Romain Colle, Emmanuelle Corruble, Nicolas Tournier, Claire Leroy, Denis J David

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Abstract

In this preclinical pilot study, we used [¹¹C]UCB-J PET imaging to monitor the synaptic modulation in depression and after fluoxetine. PET imaging was performed in a validated mouse model of depression/anxiety (CORT model), and the effect of 5-week treatment with fluoxetine was tested. Depression/anxiety phenotype and antidepressant action of fluoxetine were confirmed using the novelty-suppressed feeding test, previously validated in the CORT model. PET data showed significant decreases of volume of distribution (V _T) of [¹¹C]UCB-J in most brain regions of CORT mice compared with controls. After 5 weeks of fluoxetine, a trend toward restoration of V _T values to control levels was observed, although it reached significance only in the olfactory bulb. These preliminary data support the use of [¹¹C]UCB-J PET imaging and the CORT model to study the synaptic modulation of antidepressants. It provides excellent translational opportunities to study the relationship between synaptic plasticity and the clinical efficacy of antidepressants.

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突触囊泡2A （SV2A）正电子发射断层扫描（PET）成像作为抑郁症小鼠模型治疗反应的标志。

在这项临床前先导研究中，我们使用[11C]UCB-J PET成像来监测抑郁症和氟西汀后的突触调节。采用经验证的抑郁/焦虑小鼠模型（CORT模型）进行PET显像，并检测氟西汀治疗5周的效果。氟西汀的抑郁/焦虑表型和抗抑郁作用通过新奇性抑制喂养试验得到证实，之前在CORT模型中得到验证。PET数据显示，与对照组相比，CORT小鼠大部分脑区[11C]UCB-J的分布体积（volume of distribution, vt）显著降低。使用氟西汀5周后，观察到V - T值有恢复到控制水平的趋势，尽管仅在嗅球中达到显著性。这些初步数据支持使用[11C]UCB-J PET成像和CORT模型来研究抗抑郁药的突触调节。这为研究突触可塑性与抗抑郁药物临床疗效之间的关系提供了极好的转化机会。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Pharmacology and Translational Science Medicine-Pharmacology (medical)

CiteScore

10.00

自引率

3.30%

发文量

133

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