Brain glutathione content and glutamate uptake are reduced in rats exposed to pre- and postnatal protein malnutrition
Brain glutathione content and glutamate uptake are reduced in rats exposed to pre- and postnatal protein malnutrition
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DOI：
10.1093/jn/136.9.2357
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发表时间：
2006-09-01
影响因子：
4.2
通讯作者：
Goncalves, Carlos-Alberto
中科院分区：
文献类型：
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作者：
Feoli, Ana Maria;Siqueira, Ionara;Goncalves, Carlos-Alberto
大脑对氧化侮辱特别敏感，其抗氧化防御依赖于其谷胱甘肽含量。蛋白质营养不良(PMN)是发育过程中一种重要和非常常见的侮辱，损害体内的抗氧化防御，特别是谷胱甘肽水平。我们研究了出生前和出生后PMN是否改变了主要由星形胶质细胞(特别是谷氨酸摄取和谷氨酰胺合成)调节的大脑谷胱甘肽含量和相关的代谢途径。因此，我们测定了出生前和出生后PMN和营养对照组大鼠大脑皮质(Cx)和海马区谷胱甘肽含量、谷氨酰胺合成酶(GS)活性和谷氨酸摄取活性。虽然营养不良的大鼠在两个脑区的谷胱甘肽水平与对照组相似，但它们在出生后第2天(P2)的水平较低；在CX组，这种下降一直持续到出生后第15天。此外，我们还发现了其他变化，如P2上的总抗氧化剂活性和谷胱甘肽过氧化物酶活性降低，这些变化都没有伴随着两个脑区自由基水平或脂质过氧化的变化。此外，营养不良的大鼠血糖升高，谷氨酸摄取减少。综上所述，这些变化表明星形胶质细胞代谢的特定变化，可能与营养不良大鼠对兴奋性毒性/氧化损伤的更高易感性有关。较低的抗氧化防御能力似乎是导致氧化失衡的主要变化，而不是活性氧物种的增加。此外，尽管PMN持续存在，但改变的代谢变量可能会在成年期恢复。
The brain is particularly susceptible to oxidative insults and its antioxidant defense is dependent on its glutathione content. Protein malnutrition (PMN) is an important and very common insult during development and compromises antioxidant defenses in the body, particularly glutathione levels. We investigated whether brain glutathione content and related metabolic pathways, predominantly regulated by astrocytes (particularly glutamate uptake and glutamine synthesis), are altered by pre- and postnatal PMN in rats. Thus, we measured the glutathione content, glutamine synthetase (GS) activity, and glutamate uptake activity in the cerebral cortex (Cx) and hippocampus of rats subjected to pre- and postnatal PMN and in nourished controls. Although malnourished rats exhibited an ontogenetic profile of glutathione levels in both brain regions similar to that of controls, they had lower levels on postnatal d 2 (P2); in Cx this decrease persisted until postnatal d 15. In addition, we found other changes, such as reduced total antioxidant reactivity and glutathione peroxidase activity on P2, and these were not accompanied by alterations in free radical levels or lipoperoxidation in either brain region. Moreover, malnourished rats had elevated GS and reduced glutamate uptake. Taken together, these alterations indicate specific changes in astrocyte metabolism, possibly responsible for the higher vulnerability to excitotoxic/oxidative damage in malnourished rats. The lower antioxidant defense appears to be the main alteration that causes oxidative imbalance, rather than an increase in reactive oxygen species. Moreover, a recovery of altered metabolic variables may occur during adulthood, despite persistent PMN.