ABSTRACT
Perinatal undernutrition impairs maturational events in the development of the brain, resulting in a variety of brain dysfunctions, which affect cognitive functions. This study investigated the effects of pre- and post-natal undernutrition (diet: 8% protein; control group: 25% protein) on some glutamatergic and behavioral parameters of 21-day-old rats. In the cerebral cortex, undernutrition reduced the Na-independent [(3)H]Glutamate binding in cellular membranes and [(3)H]Glutamate vesicular uptake, without affecting the [(3)H]Glutamate uptake by slices preparation. Behavioral parameters were affected, showing a strong amnesic effect both in the short- and long-term memory of inhibitory avoidance tasks, and a significant reduction in the number of crossings in an open field. The effects of perinatal undernutrition in 21-day-old rats, which alter some glutamatergic parameters may be related to the impairment of memory in certain behavioral tasks.
Subject(s)
Avoidance Learning/physiology , Cerebral Cortex/metabolism , Exploratory Behavior/physiology , Glutamic Acid/metabolism , Malnutrition/metabolism , Age Factors , Animals , Cerebral Cortex/growth & development , In Vitro Techniques , Male , Rats , Rats, Wistar , Synaptic Vesicles/metabolism , Synaptosomes/metabolismABSTRACT
Dehydroepiandrosterone (DHEA) exerts multiple effects in the central nervous system. Most of them seem to be mediated through their nongenomic actions on neurotransmitter receptors, and these actions occur within seconds or milliseconds. DHEA increases neuronal excitability, enhances neuronal plasticity, and has neuroprotective properties. By investigating glutamate release from synaptosomes of rats at different ages (from 17 days to 12 months), we observed that (i) there is an increase in basal and K(+)-stimulated L-[3H] glutamate release in rats at 12 months old, when compared to other ages; and (ii) there is an inhibitory effect of DHEA on basal L-[3H] glutamate release in 12 months old. This inhibitory effect of DHEA could be related to its reported protective role against excitotoxicity caused by overstimulation of the glutamatergic system and ageing.
Subject(s)
Aging/metabolism , Brain/metabolism , Dehydroepiandrosterone/pharmacology , Excitatory Amino Acid Antagonists/pharmacology , Glutamic Acid/metabolism , Synaptosomes/metabolism , Animals , Dehydroepiandrosterone/administration & dosage , Dose-Response Relationship, Drug , In Vitro Techniques , Male , Osmolar Concentration , Potassium/pharmacology , Rats , Rats, WistarABSTRACT
Neurological dysfunction is common in patients with D-2-hydroxyglutaric aciduria (DHGA). However, the mechanisms underlying the neuropathology of this disorder are far from understood. In the present study, we investigated the in vitro effects of D-2-hydroxyglutaric acid (DGA) at various concentrations (0.1-1.0 mM) on various parameters of the glutamatergic system, namely the basal and potassium-induced release of L-[3H]glutamate by synaptosomal preparations, Na(+)-dependent L-[3H]glutamate uptake by synaptosomal preparations and Na(+)-independent L-[3H]glutamate uptake by synaptic vesicles, as well as of Na(+)-independent and dependent L-[3H]glutamate binding to synaptic plasma membranes from cerebral cortex of male adult Wistar rats. We observed that DGA significantly increased synaptosomal L-[3H]glutamate uptake, without altering the other parameters. Although these findings do not support a direct excitotoxic action for DGA since the metabolite did not affect important parameters of the main neurotransmission system, they do not exclude a direct action of DGA on NMDA or other glutamate receptors. More comprehensive studies are therefore necessary to evaluate the exact role of DGA on neurotransmission.
Subject(s)
Brain Diseases, Metabolic, Inborn/metabolism , Cerebral Cortex/metabolism , Glutamic Acid/metabolism , Glutarates/metabolism , Presynaptic Terminals/metabolism , Animals , Binding Sites/drug effects , Binding Sites/physiology , Brain Diseases, Metabolic, Inborn/physiopathology , Cerebral Cortex/drug effects , Cerebral Cortex/physiopathology , Disease Models, Animal , Glutarates/pharmacology , L-Lactate Dehydrogenase/metabolism , Male , Neurotoxins/metabolism , Neurotoxins/pharmacology , Presynaptic Terminals/drug effects , Rats , Rats, Wistar , Receptors, N-Methyl-D-Aspartate/drug effects , Receptors, N-Methyl-D-Aspartate/metabolism , Synaptic Transmission/drug effects , Synaptic Transmission/physiology , Synaptosomes/chemistry , Synaptosomes/metabolismABSTRACT
L-2-Hydroxyglutaric acid (LGA) accumulates and is the biochemical hallmark of the neurometabolic disorder L-2-hydroxyglutaric aciduria (LHGA). Although this disease is predominantly characterized by severe neurological findings and pronounced cerebral atrophy, the pathomechanisms of brain injury are virtually unknown. In the present study, we investigated the effect of LGA (0.1-1 mM) on various parameters of the glutamatergic system, namely the basal and potassium-induced release of L-[3H]glutamate by synaptosomal preparations, Na(+)-dependent L-[3H]glutamate uptake by synaptosomal preparations and Na(+)-independent L-[3H]glutamate uptake by synaptic vesicles, as well as of L-[3H]glutamate binding to synaptic plasma membranes from cerebral cortex of male adult Wistar rats. We observed that LGA significantly increased L-[3H]glutamate uptake into synaptosomes and synaptic vesicles, without altering synaptosomal glutamate release and glutamate binding to synaptic plasma membranes. Although more comprehensive studies are necessary to evaluate the exact role of LGA on neurotransmission, our findings do not support a direct excitotoxic action for LGA. Therefore, other abnormalities should be searched for to explain neurodegeneration of LHGA.
Subject(s)
Cerebral Cortex/physiology , Glutamic Acid/physiology , Glutarates/pharmacology , Animals , Cell Membrane/drug effects , Cell Membrane/metabolism , Cerebral Cortex/drug effects , In Vitro Techniques , L-Lactate Dehydrogenase/metabolism , Male , Nerve Tissue Proteins/metabolism , Potassium/pharmacology , Rats , Rats, Wistar , Sodium/metabolism , Synaptic Vesicles/drug effects , Synaptic Vesicles/metabolism , Synaptosomes/drug effects , Synaptosomes/metabolismABSTRACT
OBJECTIVES: Because dietary fat composition is determinant for serum cholesterol level, which is related to cardiovascular disease, we evaluated the effects of diets containing saturated (coconut oil) or polyunsaturated fatty acids (soybean oil) supplemented or not with dietary cholesterol on serum and liver lipid composition in two animal species. METHODS: Male Wistar rats (21 d old) were assigned to one of seven groups and fed with commercial diet or diets containing 5% or 20% soybean oil or 20% coconut oil with or without 1% cholesterol. Chicks were assigned to one of four groups and fed with diets containing 15% soybean oil or 15% coconut oil with or without 1% cholesterol. RESULTS: In rats, the accumulations of hepatic cholesterol and triacylglycerols were higher in the group fed 20% soybean oil and 1% cholesterol than in the group fed 20% coconut fat and 1% cholesterol. The highest serum levels of cholesterol and triacylglycerols were observed in the group fed coconut oil and cholesterol, compared with the group fed soybean oil and cholesterol. Triacylglycerol, high-density lipoprotein, and total cholesterol serum levels increased with diet containing coconut oil and cholesterol. In chicks, the highest hepatic cholesterol accumulation occurred in the group fed 15% coconut fat and 1% cholesterol. Total and high-density lipoprotein cholesterol levels increased with diet containing coconut oil and cholesterol, although none of these diets modified serum triacylglycerol levels. CONCLUSIONS: The type of experimental animal model and the diet composition influence lipid metabolism.
