Adhesion of erythrocytes to endothelial cells after acute exercise: differences in red blood cells from juvenile and adult rats.

Erythrocytes (RBC) from untrained male Wistar rats and rat glomerular endothelial cells (EC) were used to investigate the effects of acute exercise (speed: 20 m/min, slope: 0, duration: 1 hour) on RBC membrane protein oxidation and adhesion to cultured EC. Experimental animals were divided into juvenile (age 10 weeks) and adult (age 30 weeks) groups for these studies. Immediately following exercise, juvenile rat RBC membrane protein oxidation was significantly enhanced. Adult rat RBC showed significantly higher basal protein oxidation than juvenile RBC; but the level of adult rat RBC membrane protein oxidation was unaffected by exercise. Prior to exercise, adult rat RBC showed significantly higher adhesion to EC than RBC of juvenile rat. There was no difference in plasma fibronectin or fibrinogen levels following exercise. Only juvenile rat RBC showed a significant decrease in sialic acid residue content following exercise. These experiments show that there are changes in RBC-EC interactions following exercise that are influenced by animal age.

Effect of fluoxetine and cocaine on the expression of clock genes in the mouse hippocampus and striatum.

Long-term drug-induced alterations in CNS gene expression may be responsible for some therapeutic effects, such as antidepressant action, as well as for psychopathological conditions, such as drug addiction and abuse. Transcription factors called "clock" genes can be affected by psychotropic drugs and may modify the expression pattern of other genes. In this study in mice, we investigated the delayed effects of single and repeated (i.e. 14 days) administration of the antidepressant fluoxetine and the psychostimulant cocaine on the brain expression of clock genes Period1, Period2, Period3, Clock, Bmal1, Cryptochrome1, Cryptochrome2, and NPAS2 (neuronal PAS domain protein 2), and their putative target gene, serotonin N-acetyltransferase. Mice were treated at ZT05 (lights on at 5:00 am; ZT00). Brain samples (i.e. hippocampus, striatum, and prefrontal cortex) were processed for a semi-quantitative mRNA assay. Repeated but not single treatment with either drug increased serotonin N-acetyltransferase expression in all areas tested. On the other hand, the expression of clock genes was differentially affected depending on the drug (i.e. fluoxetine and cocaine), treatment schedule (i.e. single and repeated), and brain area (i.e. hippocampus and striatum) tested. More pronounced changes were induced by repeated rather than single administrations of fluoxetine or cocaine. We propose that the effects of psychoactive drugs on clock transcription factors may mediate long-term drug-induced changes, possibly by regulating the expression of a second set of genes (i.e. clock-controlled genes).

Heat shock protein 70 expression in neonatal rats after hypoxic stress.

OBJECTIVES: The tissue damage due to hypoxia in newborns is to some extent age-dependent; organs of premature babies are more vulnerable to hypoxic insult than full-term neonates. The aim of this immunohistochemical study was to investigate the role of heat shock protein 70 (HSP70), a stress-inducible protein, in developing the response to hypoxia in premature newborns. METHODS: Postnatal day-7 rats (corresponding to a human fetus of 32-34 weeks' gestation) and day-12 rats (corresponding to a full-term newborn infant) (n = 7) were subjected to mild hypoxia at 33 degrees C. Control rats (n = 7) for each group breathed room air for 4 h. After 4 h of recovery, the animals were killed, and brains, hearts and kidneys were removed for immunohistochemical staining. RESULTS: Immunohistochemically, HSP70 expression was found to be induced in the hippocampus and myocardium after exposure to hypoxia. The level of HSP70 expression in the hippocampus after hypoxic stress was significantly higher in the 12-day rats than in the 7-day rats (p = 0.03). However, HSP70 expression in the myocardium did not show any significant difference between the two groups. In addition, no significant induction of HSP70 expression was apparent in the kidney of rats exposed to hypoxia or in any organ of the control animals. CONCLUSIONS: We conclude that diminished HSP70 expression in the hippocampus of premature newborns may play a critical role in developing the response to hypoxic stress. However, HSP70 expression in the heart and the kidney after exposure to hypoxia did not appear to be related to fetal maturity.

Erythropoietin exerts neuroprotection in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated C57/BL mice via increasing nitric oxide production.

Erythropoietin (EPO), produced by the kidney and fetal liver, is a cytokine-hormone that stimulates erythropoiesis under hypoxic conditions. It has been shown that EPO is produced in the central nervous system and its receptor is expressed on neurons. Since EPO has neuroprotective effects in vitro and in vivo against brain injury, we investigated the effect of EPO treatment on locomotor activities of animals, survival of nigral dopaminergic neurons and nitrate levels in substantia nigra and striatum in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced animal model of Parkinsonism in C57/BL mice. Our findings suggest that EPO has protective and treating effect in MPTP-induced neurotoxicity in this mouse model of Parkinson's Disease via increasing nitric oxide production.

Effects of footshock stress on superoxide dismutase and glutathione peroxidase enzyme activities and thiobarbituric acid reactive substances levels in the rat prefrontal cortex and striatum.

Mild footshock stress results in an increase dopamine metabolism in the prefrontal cortex. Increases in either the intensity or duration of stress enhance dopamine metabolism in the nucleus accumbens and striatum, as well as in the prefrontal cortex. Dopamine is metabolized by monoamine oxidase with hydrogen peroxide as a product. In this study we have demonstrated that while very mild (0.2 mA) footshock stress did not change glutathione peroxidase activity in the rat prefrontal cortex and striatum, more intense (1.6 mA) footshock stress increased glutathione peroxidase activity at 0, 15, 30 and 60 min after the footshock in the prefrontal cortex and at 30 min after the footshock in the striatum. Stress did not change superoxide dismutase activity and thiobarbituric acid reactive substances levels. These results indicate that increased dopamine metabolism induced by footshock stress is probably responsible for the increase of glutathione peroxidase activity.