Chronic citalopram effects on the brain neurochemical profile and perfusion in a rat model of depression detected by the NMR techniques – spectroscopy and perfusion

IF 6.9 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Biomedicine & Pharmacotherapy Pub Date : 2024-11-01 DOI:10.1016/j.biopha.2024.117656

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引用次数: 0

Abstract

Background

Major depressive disorder (MDD) is a mental illness with a high worldwide prevalence and suboptimal pharmacological treatment, which necessitates the development of novel, more efficacious MDD medication. Nuclear magnetic resonance (NMR) can non-invasively provide insight into the neurochemical state of the brain using proton magnetic resonance spectroscopy (¹H MRS), and an assessment of regional cerebral blood flow (rCBF) by perfusion imaging. These methods may provide valuable in vivo markers of the pathological processes underlying MDD.

Methods

This study examined the effects of the chronic antidepressant medication, citalopram, in a well-validated MDD model induced by bilateral olfactory bulbectomy (OB) in rats. ¹H MRS was utilized to assess key metabolite ratios in the dorsal hippocampus and sensorimotor cortex bilaterally, and arterial spin labelling was employed to estimate rCBF in several additional brain regions.

Results

The ¹H MRS data results suggest lower hippocampal Cho/tCr and lower cortical NAA/tCr levels as a characteristic of the OB phenotype. Spectroscopy revealed lower hippocampal Tau/tCr in citalopram-treated rats, indicating a potentially deleterious effect of the drug. However, the significant OB model–citalopram treatment interaction was observed using ¹H MRS in hippocampal mI/tCr, Glx/tCr and Gln/tCr, indicating differential treatment effects in the OB and control groups. The perfusion data revealed higher rCBF in the whole brain, hippocampus and thalamus in the OB rats, while citalopram appeared to normalise it without affecting the control group.

Conclusion

Collectively, ¹H MRS and rCBF approaches demonstrated their capacity to capture an OB-induced phenotype and chronic antidepressant treatment effect in multiple brain regions.

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通过核磁共振技术--光谱学和灌注技术检测慢性西酞普兰对抑郁症大鼠模型的脑神经化学特征和灌注的影响。

背景：重度抑郁症（MDD）是一种精神疾病，在全球范围内发病率很高，但药物治疗效果并不理想，因此有必要开发更有效的新型重度抑郁症药物。核磁共振（NMR）可以通过质子磁共振波谱（1H MRS）和灌注成像评估区域脑血流（rCBF），以非侵入方式深入了解大脑的神经化学状态。这些方法可为 MDD 的病理过程提供有价值的体内标记：本研究考察了慢性抗抑郁药物西酞普兰对通过双侧嗅球切除术（OB）诱导的大鼠MDD模型的影响。利用 1H MRS 评估了双侧海马背侧和感觉运动皮层的关键代谢物比率，并利用动脉自旋标记估算了其他几个脑区的 rCBF：结果：1H MRS数据结果表明，海马Cho/tCr和皮质NAA/tCr水平较低是OB表型的特征。光谱分析显示，西酞普兰治疗的大鼠海马 Tau/tCr 水平较低，这表明该药物可能会产生有害影响。然而，使用 1H MRS 观察海马 mI/tCr、Glx/tCr 和 Gln/tCr，发现 OB 模型与西酞普兰治疗之间存在明显的交互作用，这表明 OB 组和对照组的治疗效果不同。灌注数据显示，OB 组大鼠全脑、海马和丘脑的 rCBF 较高，而西酞普兰似乎能使 rCBF 恢复正常，但对对照组没有影响：总而言之，1H MRS和rCBF方法证明了它们有能力捕捉OB诱导的表型和多个脑区的慢性抗抑郁治疗效果。

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

Biomedicine & Pharmacotherapy 医学-药学

CiteScore

11.90

自引率

2.70%

发文量

1621

审稿时长

48 days

期刊介绍： Biomedicine & Pharmacotherapy stands as a multidisciplinary journal, presenting a spectrum of original research reports, reviews, and communications in the realms of clinical and basic medicine, as well as pharmacology. The journal spans various fields, including Cancer, Nutriceutics, Neurodegenerative, Cardiac, and Infectious Diseases.