ABSTRACT
Early protein restriction during the prenatal period has significant repercussions on the ontogeny and development of the central nervous system. The present study investigates whether early prenatal protein malnutrition could alter the electrical cerebral activity of the progeny. We used Sprague-Dawley female rats of 200 g randomly divided into three groups: a control group that received a diet with 25% of the protein content (lactalbumin), the experimental group, that received a diet with 6% of the protein content and the rehabilitated group that initially received a diet with 6% of the protein content, then switched to a diet with 25% of the protein content after the weaning period (P20D) up to 60 days of life (P60D). Reduction of the protein content from 25% to 6% of lactalbumin in the diet of pregnant rats produces impairment in the electrical cerebral activity in the progeny at P20D and at P60D. The power spectral analysis for each one of the electroencephalograms revealed that prenatal protein malnutrition in rats produced a significant reduction of the alpha (8-13 Hz) and the beta bands (13-30 Hz) and a significant increase of the theta (4-8 Hz), and delta bands (1-4 Hz), at two different stages of life (P20D and P60D). Similar results were obtained for the rehabilitated group. These results indicate that early malnutrition in life affects the ontogeny of the electrical cerebral activity. This insult probably disrupts the establishment of cortical neural circuits during the critical period of brain development. The rehabilitation period did not revert the impairment in the electrical cerebral activity produced by malnutrition. We used one-way ANOVA analysis, followed by Tukey test (*p<0.001).
Subject(s)
Cerebral Cortex/growth & development , Cerebral Cortex/physiopathology , Prenatal Exposure Delayed Effects/physiopathology , Protein Deficiency/physiopathology , Animals , Electroencephalography , Female , Pregnancy , Protein Deficiency/complications , Rats , Rats, Sprague-DawleyABSTRACT
We have developed defective herpes simplex virus 1 (HSV-1) vectors, based on amplicon plasmids with a replication-deficient mutant, as helper for the transfer of the glutamic acid decarboxylase (GAD67) or beta-galactosidase (beta-gal) gene as control directed by HCMV promoter into neuronal-like cells (PC12) and primary neurons. GAD67 protein was detected immunochemically, while GAD67 activity in virus-producing and nonproducing cell lines was detected enzymatically or by GABA release. Infection with GAD67-expressing amplicon vectors enhanced the resistance of PC12 cells to H(2)O(2). This protection was related to increased energy metabolism, as shown by MTT reduction and ATP level, and involved the GABA shunt, as shown by the reduction in ATP level seen in the presence of gamma-vinyl GABA (GVG), a specific GABA transaminase inhibitor. Level of glutathione (GSH), which requires ATP for its synthesis, was increased by the GAD67 transgene. The activity of glucose-6-phosphate dehydrogenase involved in the maintenance of the NADPH that can be used for the regeneration of the GSH pool, was increased by infection with amplicon vectors. Thus, replication-deficient HSV-1 and the GAD67 transgene have complementary neuroprotective effects and infection with GAD67-expressing amplicon vectors was able to protect nondifferentiated cortical neurons from glutamate toxicity mediated by oxidative stress. Such defective GAD67-expressing HSV-1, as neurotropic vector, should be helpful in neurodegenerative diseases implicating alterations of energy metabolism and oxidative stress in neuronal cells expressing GABA transaminase.
Subject(s)
Glutamate Decarboxylase/physiology , Herpesvirus 1, Human/genetics , Isoenzymes/physiology , Neurons/physiology , Oxidative Stress/physiology , Adenosine Triphosphate/metabolism , Animals , Cell Survival/genetics , Cell Survival/physiology , Gene Transfer Techniques , Genes, Reporter/genetics , Glutamate Decarboxylase/genetics , Glutamic Acid/toxicity , Glutathione/metabolism , Heterozygote , Hydrogen Peroxide/toxicity , Isoenzymes/genetics , PC12 Cells , Plasmids/genetics , Rats , Transgenes/genetics , beta-Galactosidase/biosynthesis , beta-Galactosidase/genetics , gamma-Aminobutyric Acid/metabolismABSTRACT
Basal serotonin (5-HT) release, measured in the presence of imipramine, was significantly reduced in slices of hippocampus, n. accumbens and frontal cortex from rats subjected to forced swim test and chronic isolation. Only in the hippocampus, in the two animal models of depression, K-stimulated release was increased. In the hippocampus and frontal cortex, but not in n. accumbens, tissue content of 5-HT was reduced. This constitutes the first direct demonstration of a decreased tonic release of serotonin from different nuclei during depression. The results also suggest a nuclei specific, facilitator, presynaptic regulation of 5-HT release.
