Brain glutathione content and glutamate uptake are reduced in rats exposed to pre- and postnatal protein malnutrition

Ana Maria Feoli, Ionara Siqueira, Lucia Maria V Almeida, Ana Carolina Tramontina, Cíntia Battu, Susana T. Wofchuk, Carmem Gottfried, Marcos Luiz Perry, Carlos Alberto Gonçalves*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2357-2361
Number of pages5
JournalJournal of Nutrition
Volume136
Issue number9
DOIs
StatePublished - 2006

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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