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哺乳期过度喂养大鼠的脑干和下丘脑的 5-羟色胺能操纵的影响。

Effects of serotonergic manipulation in the brainstem and hypothalamus of overnourished rats during lactation.

机构信息

Postgraduate Program in Neuropsychiatry and Behavior Science, Federal University of Pernambuco - UFPE, Recife, PE, Brazil.

Postgraduate Program in Biochemistry and Physiology, Federal University of Pernambuco -UFPE, Recife, PE, Brazil.

出版信息

Life Sci. 2024 Dec 1;358:123179. doi: 10.1016/j.lfs.2024.123179. Epub 2024 Oct 25.

DOI:10.1016/j.lfs.2024.123179
PMID:39490520
Abstract

Previous studies suggest that being overweight and obese is capable of altering brain function during critical periods due to the higher plasticity of the brain during development. However, more literature still needs to be on the immediate effect of overnutrition and serotonin modulation in brain areas. In this study, we aimed to evaluate the effects of serotoninergic manipulation on oxidative stress and pro-inflammatory markers in the brainstem and hypothalamus of overnourished rats. The fluoxetine treatment was performed from postnatal day 3 (PND3) to postnatal day 21 (PND21) to evaluate mitochondrial function, oxidative balance, and the mRNA levels of monoaminergic molecules such as serotonin and dopamine, pro-inflammatory cytokines, and BDNF. Neonatal overnutrition induces molecular and biochemical changes in the brainstem and hypothalamus. These nutritional disturbances during lactation dysregulate energy balance and cellular redox, inducing oxidative stress. Conversely, modulation of the serotoninergic system through pharmacological use of fluoxetine was able to reverse the deleterious effects of overnutrition during lactation, enabling better brain development and delaying the development of pathologies and oxidative stress.

摘要

先前的研究表明,超重和肥胖能够在大脑发育过程中因较高的可塑性而改变关键期的大脑功能。然而,仍需要更多的文献来研究营养过剩和 5-羟色胺调节对大脑区域的即时影响。在这项研究中,我们旨在评估 5-羟色胺能操纵对超重大鼠脑干和下丘脑氧化应激和促炎标志物的影响。从出生后第 3 天(PND3)到第 21 天(PND21)进行氟西汀治疗,以评估线粒体功能、氧化平衡以及 5-羟色胺和多巴胺等单胺能分子、促炎细胞因子和 BDNF 的 mRNA 水平。新生儿营养过剩会导致脑干和下丘脑发生分子和生化变化。哺乳期的这些营养失调会扰乱能量平衡和细胞氧化还原,导致氧化应激。相反,通过使用氟西汀进行 5-羟色胺能系统的调制能够逆转哺乳期营养过剩的有害影响,从而促进大脑更好地发育,并延缓病理和氧化应激的发展。

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