title: Brain glutathione content and glutamate uptake are reduced in rats exposed to pre- and postnatal protein malnutrition.
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.
authors.affiliation: Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande de do Sul, Porto Alegre, Brazil.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Feoli
authors.forename: Ionara
authors.initials: I
authors.lastname: Siqueira
authors.forename: Lucia Maria V
authors.initials: LM
authors.lastname: Almeida
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: Tramontina
authors.forename: Cíntia
authors.initials: C
authors.lastname: Battu
authors.forename: Susana T
authors.initials: ST
authors.lastname: Wofchuk
authors.forename: Carmem
authors.initials: C
authors.lastname: Gottfried
authors.forename: Marcos Luiz
authors.initials: ML
authors.lastname: Perry
authors.forename: Carlos-Alberto
authors.initials: CA
authors.lastname: Gonçalves
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000032:analysis; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D002540:Cerebral Cortex / Q000737:chemistry / Q000378:metabolism; D005260:Female; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D005978:Glutathione / Q000032:analysis*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006624:Hippocampus / Q000737:chemistry / Q000378:metabolism; D015227:Lipid Peroxidation; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011488:Protein Deficiency / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000032:analysis
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D018698:Glutamic Acid; D005979:Glutathione Peroxidase; D005974:Glutamate-Ammonia Ligase; D005978:Glutathione