Faculty of Physics and Applied Computer Science, AGH University of Krakow, Al. Mickiewicza 30, Krakow 30-059, Poland.
Institute of Zoology and Biomedical Research, Jagiellonian University, Gronostajowa 9, Krakow 30-387, Poland.
ACS Chem Neurosci. 2024 Nov 6;15(21):3932-3944. doi: 10.1021/acschemneuro.4c00283. Epub 2024 Oct 23.
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.
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癫痫孕妇,尤其是因为大多数抗癫痫药物都有致畸作用。然而,考虑到 KD 在妊娠期间对后代的安全性,缺乏医学数据。因此,我们研究了 KD 对其后代大脑中选定区域的元素组成的影响。为此,我们利用同步辐射诱导的 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 的可能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的不同发育阶段。实验结果证实了 SR-XRF 显微镜在跟踪大脑中元素变化的巨大适用性,这些变化包括出生后发育过程中的变化和产前暴露于高脂肪饮食引起的变化。对怀孕期接受 KD 喂养的母亲所生后代的大脑进行的地形分析以及适当的对照个体表明,这种饮食处理对大脑中 P 和 S 等元素的水平有潜在影响。在最年长的后代中,注意到 P 和 S 含量增加的脑区的表面面积显著减少,这些脑区组织学/形态学上与白质结构相对应。相反,定量元素分析显示,在产前暴露于 KD 的 30 日龄大鼠的纹状体和白质中,Fe 的水平显著降低。这种影响是暂时的,在成年动物中没有注意到。观察到的异常可能与鞘磷脂和硫酸脂的积累变化有关,可能表明白质中髓鞘的结构和完整性受到干扰。