Does concomitant diazepam and ethanol use modulate age-related cognitive decline in mice?

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2024-11-05 DOI:10.1016/j.lfs.2024.123216

Louise Carton , Camille Landmann , Florent Auger , Nicolas Durieux , Charlotte Laloux , Maéva Kyheng , Maud Petrault , Kelly Timmerman , Camille Potey , Sandrine Bergeron , Julie Deguil , Régis Bordet

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引用次数: 0

Abstract

Background

Concomitant use of alcohol and benzodiazepines are described among elderly, raising concerns about their combined impact on memory. We aimed to evaluate the long-term impact of chronic diazepam use associated with ethanol intoxication on memory in aging mice.

Methods

Twelve-month-old male C57BL6 mice were assigned into 4 groups: ethanol (OH), diazepam (DIA), diazepam + ethanol (DOH) and control (CTL). For 16 weeks, ethanol was available ad libitum and diazepam was mixed with food. Behavioral testing, performed during and after treatment cessation included working memory and visual recognition memory assessment. The second session was implemented with spatial reference learning and memory assessment in the Barnes maze test. In vivo magnetic resonance spectroscopy (MRS) acquisitions were performed to quantify hippocampal metabolites during and after cessation treatment.

Results

During treatment, visual recognition memory was significantly different between groups with the DIA group exhibiting the worst performance. MRS acquisition highlighted higher glutamate and choline levels in OH and DOH groups in comparison to CTL and DIA groups. After treatment wash-out, there was no difference between in the different memories evaluated. Only the learning phase of the spatial reference memory test differed significantly with worst performance in OH groups. Three months after treatment cessation, there was no remanent effect of diazepam + ethanol on hippocampal metabolites changes.

Conclusions

We did not evidence additive effect of ethanol and diazepam on memory and hippocampal metabolite levels. The disturbances observed during treatment were no remanent, highlighting the benefits of discontinuing these substances.

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同时服用地西泮和乙醇是否会调节小鼠与年龄相关的认知能力下降？

背景：老年人中存在同时使用酒精和苯二氮杂卓的情况，这引起了人们对它们共同影响记忆的担忧。我们的目的是评估长期服用地西泮和乙醇中毒对老年小鼠记忆的长期影响：将 12 个月大的雄性 C57BL6 小鼠分为 4 组：乙醇组（OH）、地西泮组（DIA）、地西泮+乙醇组（DOH）和对照组（CTL）。在 16 周的时间里，乙醇可自由获取，地西泮则与食物混合。在停止治疗期间和之后进行的行为测试包括工作记忆和视觉识别记忆评估。第二个环节是在巴恩斯迷宫测试中进行空间参照学习和记忆评估。在停止治疗期间和之后，进行了体内磁共振光谱（MRS）采集，以量化海马代谢物：结果：在治疗期间，各组之间的视觉识别记忆存在显著差异，DIA组的表现最差。MRS 采集结果显示，与 CTL 组和 DIA 组相比，OH 组和 DOH 组的谷氨酸和胆碱水平更高。治疗结束后，不同记忆的评估结果没有差异。只有空间参照记忆测试的学习阶段存在显著差异，OH 组的表现最差。治疗停止三个月后，地西泮+乙醇对海马代谢物的变化没有再影响：结论：我们没有发现乙醇和地西泮对记忆和海马代谢物水平有叠加效应。治疗期间观察到的干扰不会再现，这突出表明了停用这些药物的益处。

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.