Stomach acid secretion in submissive and aggressive rats.

Conducted 4 experiments with 60 female and 162 male Long-Evans rats to determine whether aggressive and submissive behavior are related to either an increase or a decrease in gastric secretion. In Exp I, intruder rats placed in an established male–female colony and attacked by a dominant alpha male secreted less acid than intruders exposed to nonaggressive males and females. In Exp II, intruders exposed to attack and subsequently returned to the encounter site, but protected from physical attack, still demonstrated a gastric hyposecretion. Ss with chronic gastric cannulas in Exp III also revealed an acid inhibition when attacked and later when exposed to, but protected from, attack. Both intruders and attacking males were prepared with gastric cannulas in Exp IV. Both demonstrated secretory inhibition following attack and attack-protected sessions. The inhibitory effect was greater and more persistent for intruders than for aggressive Ss. It is suggested that the inhibition occurring during the attack-protected sessions may have been mediated by some conditioning processes, and other possible associative mechanisms, including a learning model or a direct sensory model, are discussed. (39 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Time-dependent changes in neurotrophic factor mRNA expression after kindling and long-term potentiation in rats

We compared the time-dependent changes in messenger ribonucleic acid (mRNA) levels for two neurotrophic factors after amygdala-kindled seizures and hippocampal long-term potentiation (LTP) in rats in vivo. The brain-derived neurotrophic factor (BDNF) mRNA levels in the bilateral granule cell layer of the dentate gyrus, increased significantly 1-4 h after stage 5 kindled seizures. Nerve growth factor (NGF) mRNA levels increased throughout the bilateral limbic regions more gradually than those of BDNF mRNA. The maximum levels in the dentate gyrus ipsilateral to stimulation (BDNF mRNA: 493%, NGF mRNA: 199% of control levels) occurred 2 h after seizures. As observed with kindling, BDNF and NGF mRNA expression increased in the dentate gyrus ipsilateral to stimulation also increased following LTP induced by the perforant path stimulation, with maximum levels occurring 2 h and 4 h, respectively, after stimulation, when they reached 284% and 189% of the control levels, respectively. These results suggest that BDNF and NGF are involved in enhancement of synaptic efficacy in the granule cells of the dentate gyrus in the hippocampus in kindling, not related to the neuronal excitability associated with seizure activity.     

Regulation of expression of the erythropoietin gene

Vertebral hydatid cysts are rare and found in less than 1% of all the cases of hydatidosis. Neural compression is common in vertebral hydatidosis. The prognosis is generally regarded as very poor. This paper examines the natural history and complications which may arise during the treatment of vertebral hydatid cyst, and discusses their treatment. Thirteen cases of hydatid disease affecting the vertebrae are presented. The patients were admitted with symptoms of spinal cord compression. Twelve were treated by laminectomy and one by costotransversectomy. Low back pain radiating to the legs and lower extremity weakness were the predominant symptoms. Different degrees of pareses were present in 12 patients. Nine patients had impaired sensation in lower extremities. In 13 patients, 27 operations were performed. The major complication of surgery was the death of one patient due to the formaline irrigation. The surgical goal should be an extensive removal of the cysts and affected bone. The surgical area needs to be irrigated with hypertonic saline. Mebendazole or albendazole therapy seems to retard the recurrences and control the disease.     

Tyrosine hydroxylase gene expression in the locus coeruleus of depression-model rats and rats exposed to short-and long-term forced walking stress

Abnormal brain noradrenergic function is thought to cause depressive illnesses which are sometimes manifested or aggravated under stressful conditions. To investigate the effect of chronic stress on noradrenaline (NA) synthesis in the brain we used in situ hybridization to examine the expression of tyrosine hydroxylase (TH) mRNA in the locus coeruleus (LC) of "depression-model rats" that exhibit reduced activity following exposure to long-term (14 days) forced walking stress (FWS). We also examined TH mRNA expression in rats stressed for 30 minutes, 3 hours and 1, 2 (short-term), 6 or 12 (long-term) days. The expression of TH mRNA increased markedly following 1 to 12 days of FWS, but not in rats exposed to FWS for 30 minutes or 3 hours. The expression also increased significantly in the depression-model rats, but not in the "spontaneous recovery rats" whose activity was restored after long-term stress. Our results suggest that NA synthesis remains high in the FWS-induced depression-model rats because of the high levels of TH mRNA expression in the LC. Our results also suggest that FWS is initially a mild stress but gradually becomes a severe form of unadaptable stress as reflected by delayed but persistent increases in TH mRNA expression.     

Stomach adenocarcinoma induction in rats by the combined administration of N-methyl-N-nitroso-N'-nitroguanidine precursors

N-methyl-N'-nitroguanidine and sodium nitrite were administered as drinking water to non-inbred male rats at the level of Img/ml for over two years. Gastric adenocarcinomas were produced in 43.7% of rats surviving for 15.5 months when the first tumor was noticed. Gastric mucous membrane of other rats had morphological changes analogous to those induced by N-methyl-N-nitoroso-N'-nitroguanidine (MNNG). The results obtained indicate endogenous synthesis of MNNG from precursors in the stomach of rats.     

An aldose reductase inhibitor and aminoguanidine prevent vascular endothelial growth factor expression in rats with long-term galactosemia

OBJECTIVE: To study the effects of an aldose reductase inhibitor (ARI-509, Wyeth-Ayerst, Princeton, NJ) and aminoguanidine (AMG), agents that have been reported to prevent or delay diabetic retinopathy, on retinal vascular abnormalities and the immunocytochemical expression in the retina of vascular endothelial growth factor (VEGF) in rats maintained for up to 2 years on a 50% galactose diet. METHODS: Albino rats were placed on a control diet, a diet containing 50% galactose, or the 50% galactose diet containing either ARI-509 or AMG. Treatment with ARI-509 or AMG was initiated at the beginning of the experiment or after 12 months of galactose feeding. After 22 to 24 months, the rats were killed and the retinal vasculature from half of one eye was isolated by trypsin-elastase digestion for semiquantitative evaluation of retinal vascular lesions. The other half of the retina was prepared for immunocytochemistry and stained for the presence of VEGF, factor VIII, vimentin, and glial fibrillary acidic protein. Red blood cells, sciatic nerves, and a portion of the retina from the second eye were assayed for glucose, galactose, fructose, sorbitol, galactitol, and myo-inositol. Red blood cells were also assayed for galactosylated hemoglobin. RESULTS: Galactose-fed animals developed a vascular retinopathy characterized by severe cellular loss in the retinal capillaries and intensification of periodic acid-Schiff staining of the vascular basement membranes. Some animals also displayed dilation and hypercellularity of vessels in the posterior retina. These changes were substantially reduced in animals receiving ARI-509 from the beginning of the galactose diet, but were unaffected in all of the other treatment groups. None of the rats receiving ARI-509 or AMG treatment, whether initiated from the onset or after 12 months of galactosemia, demonstrated VEGF immunoreactivity. With the exception of the animals receiving ARI-509 from the beginning of the experiment, all of the galactose-fed animals developed dense cataracts within 6 weeks of the beginning of the galactose diet. Galactitol levels in animals receiving ARI-509 were 86% to 93% lower in red blood cells, retina, and sciatic nerve than those in the other galactose-fed groups. CONCLUSIONS: Although ARI-509 and AMG have different abilities to delay or prevent the diabetic-like retinopathy in galactosemic rats, even when substantial retinal microvascular acellularity occurs, both drugs prevent the immunocytochemical expression of VEGF. These results suggest that factors other than hypoxia may be responsible for VEGF expression in the retina, and that aldose reductase inhibitors and AMG have potential roles in preventing such expression and, thus, perhaps preventing retinal neovascularization.     

Differing mechanisms of expression for short- and long-term potentiation

Long-term potentiation (LTP) is a use-dependent form of synaptic plasticity that is of great interest as a cellular mechanism that may contribute to memory storage. It is the sustained phase of population excitatory postsynaptic potential induced by high-frequency stimulation (HFS). HFS can also induce short-term potentiation (STP), a decremental potentiation lasting approximately 15 min. It has been unclear whether STP is simply a reversible form of LTP elicited by subthreshold stimuli or whether it is an independently expressed form of synaptic plasticity. We have attempted to clarify the relationship between LTP and STP in the extracellular recording technique in area CA1 of the adult rat hippocampal slice preparation to test four predictions of the hypothesis that LTP and STP are expressed via the same mechanism. First, occluding LTP expression should block STP expression. Saturating LTP under six different conditions, however, did not occlude STP expression. Second, occluding STP expression should occlude LTP expression. The partial or full occlusion of STP by two maneuvers (increasing the stimulus intensity used for HFS or applying 3-isobutyl-1-methylxanthine), however, did not occlude LTP expression. Third, LTP increases and decreases paired-pulse facilitation (PPF), and STP should have the same effect. STP did not change PFF, however. The first three results, then, suggest that STP and LTP are expressed via different mechanisms. Fourth, STP should be maximal near the LTP induction threshold, and then decrease above it. Surprisingly, STP was maximal at or very close to the LTP induction threshold, but it did not decrease above this threshold. This relationship suggests the possibility that STP and LTP share an induction step(s). What is the function of the independently expressed STP? We find that LTP can be induced by two HFSs, each of which is subthreshold for LTP, if the second is given during STP from the first. This suggests that STP can temporarily lower the LTP induction threshold. Three lines of evidence, then, suggest that STP and LTP may be expressed via different mechanisms; however, the proximity of STP saturation to LTP induction suggests that they may share an induction step(s). STP may also have the very important function of temporarily lowering the LTP induction threshold. Finally, these data suggestion caution in interpreting LTP data obtained <20-30 min after HFS, because they may be contaminated by STP, which appears to have different underlying mechanisms.     

Contextual control of long-term habituation in rats.

This study examined contextual control of long-term habituation and whether such effects are dependent on the habituating response system. Habituation of the acoustic startle response transferred from the home cage to the testing context, whereas habituation of lick suppression was context specific (Experiments 1 and 2). Contextual control of habituation was demonstrated between 2 experimental contexts for lick suppression to a tone (Experiment 3) and bar-press suppression to a light (Experiment 4). Experiment 5 extinguished habituation of lick suppression and the orienting response to a tone with 27 exposures to the habituation context. Context specificity of both responses also was found. Previous failures to demonstrate contextual control of habituation may be due to the choice of response system and to less sensitive procedures to detect response recovery. The habituation mechanism for startle is independent from the process or processes that underlie habituation in other response systems, but the nature of these mechanisms is not yet known. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pharmacokinetics of recombinant human erythropoietin in rabbits and 3/4 nephrectomized rats

We present a minimal kinetic model for excitatory synaptic transmission to cerebellar Purkinje cells. The main components are a kinetic model for a single glutamate receptor, which is calibrated with the help of patch clamp data, and a mean field approximation for the dynamics of a population of channels, which generate an EPSC. The resulting minimal model of the parallel fiber-Purkinje cell synapse is used to estimate the dynamics of glutamate in the synaptic cleft and to clarify the role of receptor desensitization in synaptic transmission. We also apply the model to different aspects of synaptic modulation, like long-term depression and potentiation by pharmacological application of ampakines. In the framework of the minimal model these effects can be understood as the result of modified receptor kinetics.     

Plasma and blood vessel endothelin-1 concentrations in hypertensive uremic rats treated with erythropoietin

The present study was designed to evaluate whether changes in plasma and blood vessel endothelin-1 (ET-1) concentrations may play a role in the enhanced blood pressure response to recombinant human erythropoietin (r-HuEPO) replacement therapy in uremia. Renal failure was induced by 5/6 nephrectomy (Nx). Uremic rats received either r-HuEPO (100 u s.c. three times a week) or the vehicle for 5 weeks. They were compared to control rats receiving the vehicle. Systolic blood pressure (tail cuff method), hematocrit, serum creatinine, plasma and tissue ET-1 were measured at the end of the protocol. Immunoreactive ET-1 (ir-ET-1) was determined by radioimmunoassay of acid-extracts from the plasma, thoracic aorta and mesenteric arterial bed. Creatinine increased about three fold in Nx animals. Blood pressure in control rats was 120+/-3 mmHg compared to 161 +/-6 mmHg in the Nx + vehicle group (p <0.01) and 199+/-9 mmHg in the Nx + r-HuEPO group (p <0.01 vs Nx + vehicle). Hematocrit in control rats was 41.3+/-0.4% vs 32.6+/-1.8% in the Nx + vehicle group (p <0.01) and 47.6+/-1.5% in the Nx + r-HuEPO group (p <0.01). Plasma ir-ET-1 levels were similar in the Nx + vehicle and Nx + r-HuEPO groups (7.9+/-1.0 and 7.8+/-0.8 pg/ml). In contrast, thoracic aorta ir-ET-1 content was significantly higher in the Nx + r-HuEPO group than in the Nx + vehicle group (20.3+/-2.9 vs 13.4+/-1.9 pg, p <0.05). Similar results were obtained in the mesenteric arterial bed. There were significant correlations between blood pressure and ir-ET-1 content in the thoracic aorta (r= 0.45, p<0.05) and in the mesenteric arterial bed (r= 0.41, p<0.05). Vascular ET-1 content but not plasma levels are increased in uremic rats treated with r-HuEPO suggesting an increase in blood vessel ET-1 production which may play a role in the pathogenesis of r-HuEPO-induced hypertension.     

Optimal erythropoietin expression in human hepatoma cell lines requires activation of multiple signalling pathways

The Drosophila wing is divided into anterior and posterior compartments, the latter characterized by the expression of the engrailed gene. A comparative analysis is presented here, and suggests that a primary conserved role of engrailed is to drive growth of limbs along the proximo-distal axis. The Apical Ectodermal Ridge in vertebrate limbs resembles the Antero/ Posterior compartment boundary in fly wings, particularly in molecular aspects. Multiple evidence suggests that the fly wing Antero/Posterior boundary is not the result of differential cell affinities between all anterior and posterior cells, but responds to the area of cell communication between anterior and posterior compartments. Arguments are presented here to support the notion that the compartment boundary is a consequence of decapentaplegic function in the control of growth. Patterning, on the other hand, requires the participation of several genes, among which are engrailed, invected and hedgehog. Finally, regulatory interactions between en/En-1 and hh/Shh may be significant in the context of morphogenetic regulation during normal development.     

Modulation of erythropoietin production by selective adenosine agonists and antagonists in normal and anemic rats

Hypoxia or anemia is the fundamental stimulus for erythropoietin (EPO) production. Recent in vitro studies suggest that EPO secretion in response to hypoxia is regulated by adenosine in the kidney. In order to examine the in vivo effect of adenosine on EPO production, we determined the effects of adenosine receptor agonists and antagonists on serum EPO concentration in normal and anemic rats. In normal rats, intravenous injection of adenosine agonists (NECA, CHA and CGS-21680) dose-dependently stimulated EPO production. Pretreatment with KW-3902, an adenosine A1 antagonist with modest A2b antagonistic action, or KF17837, an adenosine A2a antagonist, inhibited the NECA (0.1 mg/kg, i.v.)-stimulated EPO production. Anemic hypoxia, induced by 2% (v/w body weight) blood withdrawal, increased serum EPO concentration from 38 +/- 2 to 352 +/- 76 mU/ml, with the increased serum adenosine concentration in the renal vein. KF17837 (0.1 mg/kg, i.v.), but not KW-3902 (0.1 mg/kg, i.v.), inhibited the anemic hypoxia-induced increase in EPO production. The present findings support the notion that adenosine mediates the EPO production in response to hypoxia in the kidney.     

Spontaneous long-term remyelination after traumatic spinal cord injury in rats

The capability of the central nervous system to remyelinate axons after a lesion has been well documented, even though it had been described as an abortive and incomplete process. At present there are no long-term morphometric studies to assess the spinal cord (S.C.) remyelinative capability. With the purpose to understand this phenomenon better, the S.C. of seven lesionless rats and the S.C. of 21 rats subjected to a severe weight-drop contusion injury were evaluated at 1, 2, 4, 6, and 12 months after injury. The axonal diameter and the myelination index (MI = axolemmal perimeter divided by myelinated fiber perimeter) were registered in the outer rim of the cord at T9 SC level using a transmission electron microscope and a digitizing computer system. The average myelinated fiber loss was 95.1%. One month after the SC, 64% of the surviving fibers were demyelinated while 12 months later, only 30% of the fibers had no myelin sheath. The MI in the control group was 0.72 +/- 0.07 (X +/- S.D.). In the experimental groups, the greatest demyelination was observed two months after the lesion (MI = 0.90 +/- 0.03), while the greatest myelination was observed 12 months after the injury (MI = 0.83 +/- 0.02). There was a statistical difference (p < 0.02) in MI between 2 and 12 months which means that remyelination had taken place. Remyelination was mainly achieved because of Schwann cells. The proportion of small fibers (diameter = 0.5 micron or less) considered as axon collaterals, increased from 18.45% at 1 month to 27.66% a year after the contusion. Results suggest that remyelination is not an abortive phenomenon but in fact a slow process occurring parallel to other tissue plastic phenomena, such as the emission of axon collaterals.     

Reversibility of hepatic mitochondrial damage in rats with long-term cholestasis

BACKGROUND/AIMS: Long-term bile duct ligation in rats is associated with secondary biliary cirrhosis and metabolic alterations, e.g. mitochondrial dysfunction. We performed the current studies to characterize the reversibility of hepatic mitochondrial dysfunction after reversing biliary obstruction by Roux-en-Y anastomosis. METHODS: Rats were studied after 4 weeks of bile duct ligation, and after 5 or 14 days of reanastomosis. Control rats were pair-fed to treated rats and all rats were studied after starvation for 24 h. Mitochondria were isolated by differential centrifugation and enzyme activities determined by spectrophotometric methods. RESULTS: In comparison to controls, plasma beta-hydroxybutyrate concentrations were decreased in bile duct ligated rats (200+/-70 vs. 790+/-200 micromol/l) and remained decreased after relief of biliary obstruction. In contrast, plasma free fatty acids were not different between controls and treated rats. Oxidative metabolism of L-glutamate, succinate and duroquinol was decreased in liver mitochondria from bile duct ligated rats. After relief of biliary obstruction, the metabolism of L-glutamate and duroquinol normalized quickly, whereas succinate metabolism remained impaired. Similar results were obtained for the mitochondrial oxidases in disrupted mitochondria. The activities of complex I, II, III and V of the respiratory chain were reduced in bile duct ligated rats. After relief of biliary obstruction, complex I and III normalized quickly, whereas complex II and V remained impaired. Oxidative metabolism of long-chain fatty acids by isolated liver mitochondria was decreased in bile duct ligated rats and did not recover after relief of biliary obstruction. CONCLUSIONS: Long-term cholestasis in the rat is associated with a decrease in specific functions of liver mitochondria which recover only partially after Roux-en-Y anastomosis. The persistence of decreased mitochondrial fatty acid metabolism cannot be explained by impaired activity of the respiratory chain, but is more likely due to alterations in mitochondrial beta-oxidation.     

Early undernutrition impairs hippocampal long-term potentiation in adult rats.

Investigated the effects of early malnutrition on the ability to establish and maintain hippocampal long-term potentiation (LTP), a relatively permanent enhancement of synaptic and cellular responses induced by high-frequency stimulation. Six control male rats and 8 previously undernourished Ss were used in the acute preparation, and 4 controls and 6 previously undernourished Ss in the chronic preparation. Following high-frequency stimulation of hippocampal dentate granule cells, potentiation was difficult to achieve in undernourished Ss. LTP showed a significant decline within 3–6 hrs and was completely absent at 24 hrs. Further trains of stimulation resulted in only small benefits in undernourished Ss. Coupled with previously reported morphological and behavioral deficits, these findings indicate a marked hippocampal dysfunction resulting from early undernutrition and provide a potentially valuable approach for relating nutritionally induced behavioral impairments to brain function. (26 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)