Effects of prenatal exposure to 5-fluoro-2'-deoxyuridine on developing central nervous system and reproductive function in male offspring of mice

The effect of 5-fluoro-2'-deoxyuridine (FrdU) on the developing brain and postpubertal reproductive function of male mouse offspring treated prenatally was investigated. FrdU was administered intraperitoneally to pregnant ICR mice at 1.5, 3, 6, 12.5, 25, and 50 mg/kg/day on days 8 through 13 of gestation or 12.5, 25, and 50 mg/kg/day on days 14 through 18 of gestation. Dams were allowed to deliver spontaneously. Dams treated with FrdU at 12.5, 25, and 50 mg/kg/day on days 8 through 13 of gestation did not deliver because of entire intrauterine death of embryos. Male offspring were aged for 10 or 15 weeks and then cohabited with untreated female mice for assessment of reproductive performance. Histological examination of the testis, epididymis, prostate, and seminal vesicle of offspring at 12 weeks of age, and sperm analysis of offspring at 12 or 17 weeks of age were performed. Dose-dependent decreases in body weight gain were noticed throughout the life of offspring. A marked decrease in the copulation rate was noted in the group treated with FrdU at 6 mg/kg/day on days 8 through 13 of gestation. However, neither histological examination of testes and sex-accessory glands nor sperm analysis revealed adverse effects of FrdU on the reproductive function in the male offspring of dams treated with FrdU at 6 mg/kg/day on days 8 through 13 of gestation. There were no significant differences in the relative weight of testes and epididymides between the group treated with FrdU at 6 mg/kg/day on days 8 through 13 of gestation and the control group. Absolute brain weight in the groups treated with FrdU on days 8 through 13 of gestation significantly decreased, while relative brain weight increased in the group treated at 6 mg/kg/day on days 8 through 13, and at 25 and 50 mg/kg/day on days 14 through 18 of gestation. Dilatation of the lateral and third ventricles was observed in all of the male offspring of dams treated with FrdU at 6 mg/kg/day on days 8 through 13 of gestation, when inspected at 12 and 17 weeks of age. In the subsequent study, ICR mice were treated intraperitoneally with FrdU at 6.25-100 mg/kg on day 12 of gestation, and the fetuses obtained 24 h after treatment. Histological observation was performed in the ventricular zone of telencephalon, and in the ependymal and mantle layers of diencephalon in the fetal brain. The incidence of pyknotic cells in these areas was increased linearly with increasing FrdU dose. From these results and our previous findings, we suggest that damage to the central nervous system, a substantial neuronal deficit, resulting from excessive cell death in the developing brain may lead to reproductive dysfunction after puberty.     

The effects of prenatal exposure to cocaine on the dopaminergic cells in the rat retina. An immunocytochemical and neurochemical study

5-Hydroxytryptamine1A (5-HT1A) receptors have been visualized at the electron microscopic level in selected areas (dorsal raphe nucleus, hippocampus, septum) of the rat brain using specific anti-peptide antibodies. 5-HT1A receptor immunoreactivity was found almost exclusively in the somatodendritic compartment of neurons and was very rarely observed within processes possibly belonging to glial cells. The immunoenzymatic reaction product was associated exclusively with dendritic spines in the dorsal hippocampus, whereas in the dorsal raphe nucleus and the septal complex, immunoreactivity was found in both dendritic processes and somata. Although some immunolabeling was observed within the cytoplasm of cell bodies, 5-HT1A receptor immunoreactivity was essentially confined to the plasma membrane where it was unevenly distributed. It was frequently associated with synapses (except in the dorsal raphe nucleus), but was also found extrasynaptically in both somata and dendrites. These data suggest that the action of serotonin via 5-HT1A receptor could occur through junctional as well as nonjunctional transmission.     

Neurochemical and behavioural effects of neurotensin vs [D-Tyr11]neurotensin on mesolimbic dopaminergic function

Changes in bronchoalveolar lavage fluid (BALF) and blood were examined to assess the toxic effects of diborane (B2H6, CAS: 19287-45-7) on the lung. Male Wistar rats were exposed to diborane at 20 ppm (intended concentration) for 4 h (phase I study) to evaluate time-course changes up to 14 days, and at 10 or 1 ppm (intended concentrations) to assess the dose-effect relationship after 3 days (phase II study). BALF parameters [leukocyte counts, alpha 1-antitrypsin (alpha 1-AT), superoxide dismutase (SOD), total protein, phospholipids etc.] were examined and biochemical and histopathological studies were also carried out. In the phase I study, neutrophils (%) in BALF increased on the day of exposure and then decreased gradually for 3 days. Rapid and marked increases in alpha 1-AT and SOD activity in BALF were detected on the day of exposure, and phospholipids had sharply increased on day 3. After 14 days, these parameters in the exposed rats had returned to their background level and alpha 1-AT decreased significantly. In the phase II study, total protein, alpha 1-AT activity and phospholipids in BALF showed dose-dependent increases, and serum alpha 1-AT activity increased significantly. Alveolar capillary and alveolar cell damage were confirmed in rats exposed to 20 ppm, 10 ppm or 1 ppm diborane for 4 h by evaluating the parameters examined. The protection system appeared to start operating immediately after exposure, and the recovery mechanism seemed to start operating 1 day after exposure and cease by day 14. The no-observed-effect level could not be observed.     

Effects of prenatal exposure to PCBs on the neurological function of children: a neuropsychological and neurophysiological study

To determine the long-term neurotoxicity of prenatal exposure to polychlorinated biphenyls (PCBs), 54 children--27 'Yu-Cheng' ('oil disease') children and 27 controls--were administered a battery of tests, including the WISC-R, auditory event-related potentials (P300), pattern visual evoked potentials (P-VEPs) and somatosensory evoked potentials (SSEPs). Full-scale IQ scores on the WISC-R were lower for the Yu-Cheng group than for the control group. Mean P300 latencies were significantly longer, and P300 amplitude significantly more reduced, in the Yu-Cheng group than in the control group at Cz and Pz. There were no significant difference in peak latencies and amplitudes between the two groups for P-VEPs and SSEPs. These findings suggest that prenatal exposure to PCBs tends to affect high cortical function rather than the sensory pathway in the developing brain.     

Effects of prenatal exposure to N-methylpyrrolidone on postnatal development and behavior in rats

Pregnant rats (Mol:WIST) were exposed to 150 ppm N-methylpyrrolidone for 6 hours per day on gestation days 7-20. The dose level was selected so as not to induce maternal toxicity or decrease viability of offspring. In the preweaning period, the exposed offspring had a lower body weight and their physical development was delayed. Neurobehavioral evaluation of the male pups revealed no effects on basal functions of the central nervous system. The animals appeared normal and motor function (rotarod), activity level (open field), and performance in learning tasks with a low grade of complexity were similar in the two groups. However, in more difficult tasks such as the reversal procedure in Morris water maze and operant delayed spatial alternation (Skinner boxes), performance was impaired in exposed offspring.     

Effect of prenatal exposure to ethanol on intestinal development of rat fetuses

BACKGROUND: Chronic alcoholism in pregnant animals and humans lead to general growth impairment in their offspring, which show multiple birth defects and delayed grown (fetal alcohol syndrome). Here we study the maturation of the intestine under the effect of chronic exposure to ethanol in utero together with associated malnutrition. METHODS: Lactase, acid beta-galactosidase, maltase, and alkaline phosphatase activity profiles were monitored in 18-, 19-, 20-, and 21-day-old fetuses from rats kept under three nutritional treatments before and during gestation: alcohol-treated (25% ethanol in drinking water), fiber-treated (50% cellulose-diluted diet) as a control of the malnutrition associated with chronic alcoholism, and control or normal diet. Serum corticosterone determination and lactase immunolocalization were carried out. To detect possible direct effects of ethanol during the period of mucosa development, intestinal explants from 18-, 19-, and 20-day-old control fetuses were cultured either in the basal medium alone or in a medium containing 25 mM ethanol for 72, 48, and 24 h of incubation, respectively. RESULTS: Following chronic ethanol exposure in utero, intestinal weight and brush-border protein content and the specific activities of lactase, acid beta-galactosidase, maltase, and alkaline phosphatase were significantly lower than those of nutritional controls. Organ culture results, under the assay conditions stated, did not show a direct effect of ethanol 25 mM on prenatal mucosal functionality. CONCLUSIONS: All these results suggest that maternal malnutrition is not primarily responsible for the impaired intestinal maturation in rat fetuses from alcohol-treated mothers; indirect effects of ethanol and/or its derivatives throughout embryo-fetal development could be necessary to promote this intestinal delay.     

Effects of prenatal ethanol exposure on parvalbumin-expressing GABAergic neurons in the adult rat medial septum

Exposure of human fetuses to ethanol often results in the fetal alcohol syndrome. Animal models of fetal alcohol syndrome have been developed and used to examine the consequences of prenatal ethanol exposure on the central nervous system. The objective of this study was to determine the long-term effects of prenatal ethanol exposure on parvalbumin-expressing (PA+) GABAergic neurons of the rat medial septum. Pregnant Long-Evans rats were maintained on 1 of 3 diets from gestational day 0 to 21: an ethanol-containing liquid diet in which ethanol accounted for 35% of the total calories, a similar diet with the isocaloric substitution of sucrose for ethanol, or a lab chow control diet. Offspring were killed on postnatal day 60, and their brains were prepared for parvalbumin immunocytochemistry. Female rats exposed to the ethanol-containing diet during gestation had 42% fewer PA+ neurons in the medial septum and reduced PA+ cell density when compared with female rats exposed to the sucrose diet. Ethanol females also had fewer PA+ neurons per unit volume than sucrose females. Male rats exposed to ethanol did not display a similar reduction in PA+ neurons or density. No effect of prenatal diet was found on the area or volume of the medial septum, nor were cell diameters affected. As such, prenatal exposure to ethanol seems to reduce permanently the number of PA+ neurons in the female rat medical septum without affecting area, volume, or neuronal size. Functional implications and possible relations to the fetal alcohol syndrome are discussed.     

Effects of prenatal alcohol exposure on the postnatal morphology of the rat oculomotor nucleus

Morphological development of the rat oculomotor nucleus was investigated on postnatal day 15 following a prenatal ethanol exposure. Analysis of toluidine blue stained plastic sections showed that the prenatal alcohol exposure caused a decrease in the density of neurons and an increase in the density of astrocytes in the center of the nucleus. There was an alcohol-induced reduction in the overall size of the cross-sectional region of the oculomotor nucleus, but no effect on the number of neurons per unit area of that total oculomotor region, indicating a delay or alteration of the migration of neurons to their normal clustered position in the center of the nucleus. The areas of the neuronal cell nucleus and nucleolus were not affected by the alcohol exposure. Analysis of Golgi-Cox-impregnated multipolar neurons showed that the alcohol exposure caused a reduction in area of the cell soma; a reduction in the number of dendritic branches; and a reduction in the complexity of the dendritic arbor relative to distance from the soma, based on concentric ring analysis. The results of this study demonstrate that gestational alcohol exposure can retard the maturation of the oculomotor nucleus.     

The effect of intermittent carbon monoxide exposure on experimental atherosclerosis in the rabbit

(1) Twenty-four female New Zealand White rabbits were fed commercial diet plus 2% cholesterol. Twelve of these animals were exposed to carbon monoxide for 4 hours per day, seven days per week for 10 weeks. The carbon monoxide exposure was such that the mean blood carboxy-haemoglobin was raised to approximately 20% during each exposure period. Twelve control animals breathed atmospheric air under the same conditions of confinement as the carbon monoxide-exposed group. (2) No significant differences in the plasma levels of cholesterol, triglycerides or glutamate oxalacetate transaminase were observed between the two groups during the experiment. (3) When the animals were sacrificed at the end of the experiment no significant differences were observed between the two groups in the aortic content of triglycerides, cholesterol or phospholipids. (4) The extent of coronary artery atherosclerosis was statistically significantly higher in the carbon monoxide group than in the control group. (5) Ultracentrifugal analysis of plasma lipoproteins revealed that there was significantly more cholesterol in the d less than l.006 fraction from the CO-exposed rabbits. (6) These findings, are discussed with particular reference to the claim that the causal agent in tobacco smoke associated arterial disease is carbon monoxide.     

High and low responders to novelty and mesolimbic noradrenaline: Effects of noradrenergic agents on radial-maze performance.

The authors used high and low responders to novelty (HRs and LRs, respectively) to examine the effects of noradrenergic injections into the nucleus accumbens using a special radial-maze task. During the 5 successive test days, solvent-treated HRs acquired this task faster than LRs. Isoproterenol (β-agonist) combined with phenylephrine (α-agonist) improved acquisition in LRs but not in HRs; this effect was counteracted by propranolol (β-antagonist) and phentolamine (α-antagonist). Propranolol combined with phentolamine, as well as phentolamine alone, disrupted acquisition in HRs but not in LRs. Data show that the effects of noradrenergic agents in HRs and LRs are due to differences in acquisition directed by type-specific differences in functional mesolimbic noradrenaline. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Influence of prenatal exposure to low levels of lead on the neuro-behavioral development of neonates

OBJECTIVES: To study the effects on the neuro-behavioral development of neonates exposed to low levels of lead in utero. METHODS: 131 neonates were selected and their umbilical blood lead level was determined by Atomic Absorption Spectrometer. The neurobehavioral-cognitive performance of neonates was evaluated by Neonatal Behavioral Neurological Assessment (NBNA). RESULTS: NBNA scores in neonates with blood lead levels greater than or equal to 0.29 mumol/L were markedly lower than those with less than 0.14 mumol/L, and the difference was highly significant. CONCLUSION: Blood lead levels of less than 0.48 mumol/L could still have harmful effects on the development of children.     

Relationship of Type A behavior pattern in smokers to carbon monoxide exposure and smoking topography.

Compared exposure to cigarette smoke in 42 graduate and undergraduate student smokers assessed for the Type A behavior pattern. After controlling for smoking rate and cigarette carbon monoxide yield, Type As' alveolar carbon monoxide (COa) levels were higher than Type Bs', and Jenkins Activity Survey scores were correlated with COa. To determine the source of this difference, smoking topography was measured in 10 Type As and 10 Type Bs. Results suggest that consummatory behaviors of Type As may help account for the Type A–coronary heart disease relationship for smokers. Due to increased smoke exposure, Type A smokers may also be at greater risk for cancer and lung disease. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of prenatal exposure to cocaine on conditional discrimination learning in adult rats.

Adult male rats that were gestationally exposed to cocaine and control offspring were trained on an instrumental conditioning task for assessment of the acquisition and reversal of an appetitive conditional discrimination based on olfactory cues. Offspring were derived from Sprague-Dawley dams that had received subcutaneous/ly (sc) injections of 40 mg/kg/3 cc cocaine hydrochloride (C40) daily on Gestational Days 8–20, pair-fed (PF) dams that were injected with saline, nutritional control dams (NC) that received saline injections, and nontreated control dams (LC). There were no differences among the prenatal treatment groups in acquisition of the barpress response or response rate throughout all phases of training. All prenatal treatment groups required approximately the same number of sessions to criterion on the initial odor discrimination. In contrast, adult C40 offspring required more sessions to acquire the reversal of the conditional discrimination than did animals from the other treatment groups (PF, NC, and LC). In addition, even at criterion performance for acquisition of the reversal discrimination, C40 animals exhibited lower accuracy on the 1st 10 responses and made significantly more errors before the 1st reward. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Developmental and behavioral effects of prenatal primidone exposure in the rat

Pregnant Sprague-Dawley rats were administered primidone (PRM) by oral gavage on gestation days 8-17 in doses of 0.40, and 80 mg/kg. Although these doses of PRM did not produce significant differences in litter size, birth weight, mortality, date of attainment of developmental landmarks or measures of preweaning reflex and motor development, there were a number of significant differences that developed as the animals approached and entered adulthood. When tested as adults, the 80 mg/kg male rats showed a deficit in the performance of an eight-arm radial maze task. These same animals showed a significant reduction in open field activity when tested as adults. In addition, both male and female PRM-treated animals showed reduced body weights at different periods corresponding to onset of sexual maturation during development. These findings are consistent with the larger body of literature reporting on the neurobehavioral teratology of phenobarbital, including its ability to produce lesions in the hippocampus and endocrine dysfunction resulting in reproductive deficits. These results suggest that PRM produces its adverse effects as a result of its metabolism to phenobarbital, which in turn affects the limbic system.     

Effect of prenatal and postnatal exposure to ethanol on rat central nervous system gangliosides and glycosidases

We investigated the effect of maternal alcohol consumption on cell number, gangliosides and ganglioside catabolizing enzymes in the central nervous system (CNS) of the offspring. Virgin female rats of the Charles Foster strain were given 15% (v/v) ethanol in drinking water one month prior to conception and during gestation and lactation. At 21 days postnatal age, the offspring were sacrificed and the brains were separated into cerebrum, cerebellum and brain stem to investigate possible regional variations. Compared to controls, wet weight of cerebrum, cerebellum and brain stem, and of spinal cord was decreased in the pups exposed to alcohol. DNA and protein contents were also found to be lowered in all the CNS regions of the pups exposed to alcohol. Conversely, maternal alcohol consumption was found to increase the concentration and the content of total ganglioside N-acetyl-neuraminic (NANA) in CNS of the pups. In addition, alcohol treatment was found to induce alterations in the proportions of individual ganglioside fractions. Interestingly, these alterations are somewhat different than those observed in the neonatal brain and spinal cord of the pups subjected to prenatal alcohol exposure. The alterations in the proportions of ganglioside fractions were shown to be region-specific. Maternal alcohol consumption resulted in decreased activities of sialidase, beta-galactosidase, beta-glucosidase and beta-hexosaminidase. The results suggest that the alcohol-associated increases in ganglioside concentration may be at least partly due to the decreased activities of ganglioside catabolizing enzymes.     

Long-term effects of prenatal exposure to low levels of gamma rays on open-field activity in male mice

The open-field activity of first-generation (F1) hybrid male C57BL/6 x C3H mice irradiated with gamma rays on day 14 of gestation was studied at the following ages: 6-7 months (young), 12-13 months (adult) and 19-20 months (old). Doses were 0.5 Gy or 1.0 Gy. Open-field activity was recorded with a camera. The camera output signal was recorded every second through an A/D converter to a personal computer. The field was divided into 25 8-cm2 units. All recordings were continuous for 60 min. The walking speed of the 1.0-Gy group recorded at 19-20 months was higher than that for the comparably aged control group. The time which the irradiated group, recorded at 19-20 months, spent in the corner fields was high in comparison with the control group at the same age. Conversely, the time spent by the irradiated group in the middle fields when recorded at 19-20 months was shorter than in the comparably aged control group. No effect of radiation was shown for any of the behaviors observed and recorded at 6-7 and 12-13 months. The results demonstrate that such exposure to gamma rays on day 14 of gestation results in behavioral changes which occur at 19-20 months but not at 6-7 or 12-13 months.     

Effects of lead exposure on licking and yawning behaviour in rats

Most studies on facial trauma in the pediatric age group focus on special subgroups. This investigation encompasses all traumatic facial injuries, minor and major, of children and adolescents. Epidemiological data of the type and pattern of injury of trauma patients less than 19 years of age, treated during a 3-year-period in a large metropolitan trauma centre were reevaluated. Of the 1385 patients, 68% had soft tissue injuries, 24% had dental trauma, and 8% fractures of facial bones. More than 90% suffered from minimal or minor trauma. The leading cause of injury was a fall, predominantly at the toddler stage. In adolescents an adult mechanism of trauma prevailed: over 60% of injuries were sequelae of an assault or altercation. The male sex predominated through all age groups and for all types of injuries. The bulk of soft tissue injuries are located within a small falling zone, extending from the nose to the mental area. There was a rising incidence of fractures of facial bones towards older age groups, mandibular fractures being the most common. Condylar fractures, with their potential impact on further growth of the mandible, are seen frequently in children and adolescents, making up 80% of the fractures of the lower jaw.     

Effects of prenatal exposure to cocaine on Morris water maze performance in adult rats.

The spatial memory of adult rats prenatally exposed to cocaine and that of control offspring was assessed using the Morris water maze. Offspring were derived from Sprague Dawley dams that received subcutaneous injection of 40 mg/kg/3 cc cocaine hydrochloride (C40) daily on gestational Days 8-20, pair-fed dams injected with saline, or nontreated control dams. After acquisition, the platform was moved to a new location (reversal phase). Probe trials were conducted at the end of acquisition and reversal training. On the 1st acquisition day, adult male and female offspring prenatally exposed to cocaine required significantly more time and traversed a greater distance to find the hidden platform than did control offspring. Despite these initial differences observed in C40 offspring performance, all of the rats were performing at equivalent levels at the time probe trials were conducted. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The diffusion of carbon into tungsten and molybdenum at low carbon concentrations

Summary The principal diffusion constants of carbon — the preexponential factor D₀ and the energy of activation of the process, Q — have been determined with the aid of the isotope C¹⁴.As a result of annealing for 3.5 h in the temperature range 1100–1450°C, carbon was found to penetrate into tungsten and molybdenum to depths of 5 and 40 , respectively.