Element Changes Occurring in Brain Point at the White Matter Abnormalities in Rats Exposed to the Ketogenic Diet During Prenatal Life.

IF 4.1 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY ACS Chemical Neuroscience Pub Date : 2024-11-06 Epub Date: 2024-10-23 DOI:10.1021/acschemneuro.4c00283
Marzena Rugieł, Zuzanna Setkowicz, Mateusz Czyzycki, Rolf Simon, Tilo Baumbach, Joanna Chwiej
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Abstract

A large number of clinical studies demonstrate that the ketogenic diet (KD) may be an effective approach to the reduction of epileptic seizures in children and adults. Such dietary therapy could also help pregnant women with epilepsy, especially since most antiseizure drugs have teratogenic action. However, there is a lack of medical data, considering the safety of using KD during gestation for the progeny. Therefore, we examined the influence of KD used prenatally in rats on the elemental composition of the selected brain regions in their offspring. For this purpose, synchrotron radiation-induced X-ray fluorescence (SR-XRF) microscopy was utilized, and elements such as P, S, K, Ca, Fe, and Zn were determined. Moreover, to verify whether the possible effects of KD are temporary or long-term, different stages of animal postnatal development were taken into account in our experiment. The obtained results confirmed the great applicability of SR-XRF microscopy to track the element changes occurring in the brain during postnatal development as well as those induced by prenatal exposure to the high-fat diet. The topographic analysis of the brains taken from offspring of mothers fed with KD during pregnancy and appropriate control individuals showed a potential influence of such dietary treatment on the brain levels of elements such as P and S. In the oldest progeny, a significant reduction of the surface of brain areas characterized by an increased P and S content, which histologically/morphologically correspond to white matter structures, was noticed. In turn, quantitative elemental analysis showed significantly decreased levels of Fe in the striatum and white matter of 30-day-old rats exposed prenatally to KD. This effect was temporary and was not noticed in adult animals. The observed abnormalities may be related to the changes in the accumulation of sphingomyelin and sulfatides and may testify about disturbances in the structure and integrity of the myelin, present in the white matter.

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产前摄入生酮饮食的大鼠脑部发生的元素变化指向白质异常。
大量临床研究表明,生酮饮食(KD)可能是减少儿童和成人癫痫发作的有效方法。这种饮食疗法也可以帮助患有癫痫的孕妇,特别是因为大多数抗癫痫药物都有致畸作用。然而,考虑到在妊娠期间使用 KD 对胎儿的安全性,目前还缺乏医学数据。因此,我们研究了大鼠产前使用 KD 对其后代选定脑区元素组成的影响。为此,我们利用同步辐射诱导 X 射线荧光(SR-XRF)显微镜测定了 P、S、K、Ca、Fe 和 Zn 等元素。此外,为了验证 KD 可能产生的影响是暂时的还是长期的,我们在实验中考虑了动物出生后发育的不同阶段。所获得的结果证实,SR-XRF 显微镜非常适用于追踪产后发育过程中大脑中发生的元素变化,以及产前暴露于高脂肪饮食所诱发的元素变化。对母亲在怀孕期间喂食 KD 的后代和适当对照组的大脑进行的地形分析表明,这种饮食处理对大脑中 P 和 S 等元素的含量有潜在影响。反过来,定量元素分析表明,产前暴露于 KD 的 30 天大老鼠纹状体和白质中的铁含量明显下降。这种影响是暂时的,在成年动物中没有发现。观察到的异常情况可能与鞘磷脂和硫化物的积累变化有关,并可能证明白质中存在的髓鞘的结构和完整性受到了干扰。
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来源期刊
ACS Chemical Neuroscience
ACS Chemical Neuroscience BIOCHEMISTRY & MOLECULAR BIOLOGY-CHEMISTRY, MEDICINAL
CiteScore
9.20
自引率
4.00%
发文量
323
审稿时长
1 months
期刊介绍: ACS Chemical Neuroscience publishes high-quality research articles and reviews that showcase chemical, quantitative biological, biophysical and bioengineering approaches to the understanding of the nervous system and to the development of new treatments for neurological disorders. Research in the journal focuses on aspects of chemical neurobiology and bio-neurochemistry such as the following: Neurotransmitters and receptors Neuropharmaceuticals and therapeutics Neural development—Plasticity, and degeneration Chemical, physical, and computational methods in neuroscience Neuronal diseases—basis, detection, and treatment Mechanism of aging, learning, memory and behavior Pain and sensory processing Neurotoxins Neuroscience-inspired bioengineering Development of methods in chemical neurobiology Neuroimaging agents and technologies Animal models for central nervous system diseases Behavioral research
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