Late pregnancy maternal naringin supplementation affects the mitochondria in the cerebellum of Wistar rat offspring via sirtuin 3 and AKT

IF 1.7 4区 医学 Q3 DEVELOPMENTAL BIOLOGY
Bernardo Gindri dos Santos, Pauline Maciel August, Débora Santos Rocha, Ismael Mesquita, Manuela Menegotto, Vinícius Stone, Cristiane Matté
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Abstract

Dietary polyphenol consumption is associated with a wide range of neuroprotective effects by improving mitochondrial function and signaling. Consequently, the use of polyphenol supplementation has been investigated as an approach to prevent neurodevelopmental diseases during gestation; however, the data obtained are still very inconclusive, mostly because of the difficulty of choosing the correct doses and period of administration to properly prevent neurodegenerative diseases without undermining normal brain development. Thus, we aimed to evaluate the effect of naringin supplementation during the third week of gestation on mitochondrial health and signaling in the cerebellum of 21-day-old offspring. The offspring born to naringin-supplemented dams displayed higher mitochondrial mass, membrane potential, and superoxide content in the cerebellum without protein oxidative damage. Such alterations were associated with dynamin-related protein 1 (DRP1) and phosphorylated AKT (p-AKT) downregulation, whereas the sirtuin 3 (SIRT3) levels were strongly upregulated. Our findings suggest that high dietary polyphenol supplementation during gestation may reduce mitochondrial fission and affect mitochondrial dynamics even 3 weeks after delivery via SIRT3 and p-AKT. Although the offspring born to naringin dams did not present neurobehavioral defects, the mitochondrial alterations elicited by naringin may potentially interfere during neurodevelopment and need to be further investigated.

Abstract Image

孕晚期母体补充柚皮苷可通过sirtuin 3和AKT影响Wistar大鼠后代小脑的线粒体。
通过改善线粒体功能和信号传导,摄入膳食多酚具有广泛的神经保护作用。因此,研究人员将补充多酚作为预防妊娠期神经发育疾病的一种方法;然而,所获得的数据仍很不确定,这主要是因为很难选择正确的剂量和给药时间,以在不破坏正常大脑发育的情况下适当预防神经退行性疾病。因此,我们旨在评估在妊娠第三周补充柚皮苷对 21 天大的后代小脑线粒体健康和信号转导的影响。补充柚皮苷的母体所生后代的小脑线粒体质量、膜电位和超氧化物含量均有所提高,但未出现蛋白质氧化损伤。这种变化与达因明相关蛋白 1(DRP1)和磷酸化 AKT(p-AKT)的下调有关,而 sirtuin 3(SIRT3)的水平则强烈上调。我们的研究结果表明,在妊娠期间补充大量多酚可能会减少线粒体裂变,甚至在分娩后 3 周也会通过 SIRT3 和 p-AKT 影响线粒体动力学。虽然柚皮苷母体所生的后代没有出现神经行为缺陷,但柚皮苷引起的线粒体变化可能会干扰神经发育,需要进一步研究。
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来源期刊
CiteScore
3.30
自引率
5.60%
发文量
78
审稿时长
6-12 weeks
期刊介绍: International Journal of Developmental Neuroscience publishes original research articles and critical review papers on all fundamental and clinical aspects of nervous system development, renewal and regeneration, as well as on the effects of genetic and environmental perturbations of brain development and homeostasis leading to neurodevelopmental disorders and neurological conditions. Studies describing the involvement of stem cells in nervous system maintenance and disease (including brain tumours), stem cell-based approaches for the investigation of neurodegenerative diseases, roles of neuroinflammation in development and disease, and neuroevolution are also encouraged. Investigations using molecular, cellular, physiological, genetic and epigenetic approaches in model systems ranging from simple invertebrates to human iPSC-based 2D and 3D models are encouraged, as are studies using experimental models that provide behavioural or evolutionary insights. The journal also publishes Special Issues dealing with topics at the cutting edge of research edited by Guest Editors appointed by the Editor in Chief. A major aim of the journal is to facilitate the transfer of fundamental studies of nervous system development, maintenance, and disease to clinical applications. The journal thus intends to disseminate valuable information for both biologists and physicians. International Journal of Developmental Neuroscience is owned and supported by The International Society for Developmental Neuroscience (ISDN), an organization of scientists interested in advancing developmental neuroscience research in the broadest sense.
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