ABSTRACT
It is widely known that a complex interaction between excitatory and inhibitory systems is required to support the adequate functioning of the brain and that significant alterations induced by early protein restriction are complex, involving many systems. Based on such assumptions, we investigated the effects of maternal protein restriction during pregnancy and lactation followed by offspring protein restriction on some GABAergic and glutamatergic parameters, which mediate inhibitory and excitatory transmission, respectively. The sensitivity of young malnourished rats to convulsant actions of the GABA(A) receptor antagonist picrotoxin (PCT; s.c.) and to N-methyl-d-aspartate (NMDA) receptor agonist quinolinic acid (QA; i.c.v) and also gamma-amino-n-butyric acid (GABA) and glutamate uptake by cortical and hippocampal slices were evaluated in P25 old rats. Early protein malnutrition induced higher sensitivity to picrotoxin, which could be associated with the observed higher GABA uptake by cortical, and hippocampal slices in malnourished rats. In contrast, we observed lower sensitivity to quinolinic acid in spite of unaltered glutamate uptake by the same cerebral structures. Picrotoxin enhanced GABA uptake in hippocampus in well- and malnourished rats; however, it did not affect cortical GABA uptake. Our data corroborate our previous report, showing that malnutrition depresses the glutamatergic activity, and point to altered modulation of GABAergic neurotransmission. Such findings allow us to speculate that malnutrition may affect the excitatory and inhibitory interaction.
Subject(s)
Cerebral Cortex/drug effects , Fetal Nutrition Disorders/pathology , Hippocampus/drug effects , Picrotoxin/pharmacology , Quinolinic Acid/pharmacology , gamma-Aminobutyric Acid/metabolism , Analysis of Variance , Animals , Animals, Newborn , Body Weight/drug effects , Caseins/pharmacology , Cerebral Cortex/metabolism , Dose-Response Relationship, Drug , Excitatory Amino Acid Agonists/pharmacology , Female , GABA Antagonists/pharmacology , Glutamic Acid/metabolism , Hippocampus/metabolism , In Vitro Techniques , Lactation , Male , Pregnancy , Prenatal Nutritional Physiological Phenomena , Rats , Seizures , Time Factors , Tritium/metabolismABSTRACT
We investigated the effect of high (12, 20, and 50 mM) extracellular K+ concentrations ([K+]0) on [U-14C] acetate oxidation to CO2 in cerebral cortex slices of control and perinatal malnourished rats. High [K+]o increased the acetate oxidation, compared with a medium containing 2.7 mM [K+]0. By investigating the mechanisms involved in this stimulation, it was shown that (i) ouabain (1 mM) and monensin (10 microM) prevented this increase; (ii) in a medium with physiological [K+]0 (2.7 mM), the decreasing of [Na+]0 stimulated acetate oxidation. These results suggest that the stimulatory effect of [K+]0 on acetate oxidation was due to the decreasing of Na1 levels. Considering that malnutrition could alter the activity of Na+,K(+)-ATPase and/or other pertinent proteins, its effect on acetate oxidation was investigated. The malnutrition, which altered the body and cerebral weight of rats, did not modify the acetate oxidation in any protocol.
