RESUMEN
AIM: The present study examines in particular associative learning and aversive memory abilities in adult Sprague Dawley rats exposed to all-trans retinoic acid (ATRA) in the period spanning gestational days (GD) 11-13. MATERIALS AND METHODS: The ATRA dosage of 2.5 mg/kg compatible with high neonatal survival, sufficient to supply offspring for later behavioral testing, was used. RESULTS: The results show that the GD 11-13 ATRA exposure compromises the ability of rats to learn an active avoidance task. Indeed, unlike control rats, the ATRA-treated rats did not improve in performance over blocks of training, the number of attempts they made to avoid foot shock being significantly affected. The memory ability, assessed with the passive avoidance paradigm, was not affected by ATRA exposure. CONCLUSIONS: The results provide further evidence that, beyond gross CNS malformations, gestational ATRA exposure induces long-term cognitive deficits in the offspring, thus raising further warning for better control of retinoid safety during pregnancy, an aspect relevant to human health protection within the regulatory environment.
Asunto(s)
Antineoplásicos/efectos adversos , Trastornos del Conocimiento/inducido químicamente , Efectos Tardíos de la Exposición Prenatal , Tretinoina/efectos adversos , Animales , Reacción de Prevención/efectos de los fármacos , Embrión de Mamíferos , Femenino , Masculino , Memoria/efectos de los fármacos , Embarazo , Ratas Sprague-Dawley , Reproducción/efectos de los fármacosRESUMEN
Studies dealing with the outcomes of developmental carbon monoxide (CO) exposure on myelination in rat offspring are reviewed. Prenatal CO exposure from gestational day 0 to gestational day 20 impairs myelin deposition around peripheral axons resulting in a significant hypomyelination in juvenile and adult rats. Myelin protein patterns analyzed by SDS-polyacrylamide gel electrophoresis and lipid patterns analyzed by the HPTLC method are not altered in both peripheral and central nervous systems of CO-exposed offspring. Interestingly, when sphingomyelin is extracted and purified, the derivatization by OPA reagent and analysis by reversed-phase HPLC reveal a significant increase in sphingosine levels in peripheral nervous system but not in central nervous system of CO-exposed rats. The above morphological and biochemical alterations are not accompanied by motor disabilities.
Asunto(s)
Enfermedades del Sistema Nervioso Periférico/epidemiología , Complicaciones del Embarazo/epidemiología , Fumar/epidemiología , Animales , Femenino , Humanos , Embarazo , Factores de RiesgoRESUMEN
Contrasting studies on the toxic effects of sodium fluoride (NaF) during developmental stages of Wistar rats, lead us to investigate the neurofunctional effects caused by its perinatal exposure, devoid of any overt sign of toxicity and/or gross malformation. NaF solution was administered to pregnant rats by intragastric gavage at a daily dose of 2.5 and 5.0 mg/kg from gestational day 0 to day 9 after parturition. Developmental NaF exposure caused sex and dose specific behavioural deficits which affected males more than females in the majority of the evaluated end-points. In particular, the perinatal exposure to NaF 5.0 mg/kg, significantly affected learning, memory, motor coordination and blood pressure only in male rats. Conversely, a lack of habituation upon the second presentation of the objects and failure in the ability to discriminate between the novel and the familiar object were observed only in NaF 5.0 mg/kg female rats. Finally, a significant impairment of sexual behaviour was observed in male rats at both NaF dose levels. The present data indicate that perinatal rat exposure to NaF results in long lasting functional sex-specific alterations which occur at fluoride levels approaching those experienced by offspring of mothers.
Asunto(s)
Conducta Animal/efectos de los fármacos , Cariostáticos/toxicidad , Efectos Tardíos de la Exposición Prenatal , Fluoruro de Sodio/toxicidad , Animales , Reacción de Prevención/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Conducta Exploratoria/efectos de los fármacos , Femenino , Edad Gestacional , Habituación Psicofisiológica/efectos de los fármacos , Masculino , Memoria/efectos de los fármacos , Embarazo , Desempeño Psicomotor/efectos de los fármacos , Ratas , Ratas Wistar , Medición de Riesgo , Factores Sexuales , Conducta Sexual Animal/efectos de los fármacos , Factores de Tiempo , Vocalización Animal/efectos de los fármacosRESUMEN
The neurobehavioral and neurochemical effects produced by prenatal methylmercury exposure (8 mg/kg, gestational-days 8 or 15), were investigated in rats. On postnatal day 40, animals exposed to methylmercury and tested in the open field arena, showed a reduction in the number of rearings, whereas the number of crossings and resting time was not altered with respect to the age-matched control rats. The methylmercury-exposed groups showed a lower level of exploratory behavior as well as an impairment in habituation and working memory when subjected to the novel object exploration task. The neophobia displayed by methylmercury-exposed rats is unlikely to be attributed to a higher degree of anxiety. Prenatal methylmercury exposure did not affect motor coordination or motor learning in 40-day-old rats subjected to the balance task on a rotating rod, and it did not impair the onset of reflexive behavior in pups screened for righting reflex, cliff aversion and negative geotaxis. In cortical cell cultures from pups exposed to methylmercury during gestation, basal extracellular glutamate levels were higher, whereas the KCl-evoked extracellular glutamate levels were lower than that measured in cultures from rats born to control mothers. In addition, a higher responsiveness of glutamate release to N-methyl-D-aspartic acid receptor activation was evident in cortical cell cultures from pups born from methylmercury-treated dams than in cultures obtained from control rats. The present results suggest that acute maternal methylmercury exposure induces, in rat offspring, subtle changes in short-term memory as well as in exploratory behavior. These impairments seem to be associated to alterations of cortical glutamatergic signaling.
Asunto(s)
Conducta Animal/efectos de los fármacos , Química Encefálica/efectos de los fármacos , Compuestos de Metilmercurio/toxicidad , Actividad Motora/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal , Reflejo de Sobresalto/efectos de los fármacos , Análisis de Varianza , Animales , Animales Recién Nacidos , Peso Corporal/efectos de los fármacos , Células Cultivadas , Corteza Cerebral/citología , Agonistas de Aminoácidos Excitadores/farmacología , Conducta Exploratoria/efectos de los fármacos , Femenino , Ácido Glutámico/metabolismo , Inhibición Psicológica , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , N-Metilaspartato/farmacología , Neuronas/efectos de los fármacos , Cloruro de Potasio/farmacología , Embarazo , Ratas , Ratas Sprague-Dawley , Prueba de Desempeño de Rotación con Aceleración Constante/métodos , Factores de TiempoRESUMEN
Due to its structural similarity with sphingosine, fumonisin B(1) (FB(1)) inhibits ceramide synthase (a key enzyme of sphingolipid biosynthesis) leading to an intracellular accumulation of sphingoid bases with a consequent increase of sphinganine/sphingosine (SA/SO) ratio. In adult male rats, dietary exposure to fumonisin induces a significant increase in both SA concentrations and SA/SO ratio in kidney, but not in liver and brain, as well as a significant reduction of body weight gain. Regarding the brain, the developing rat is more sensitive to FB(1) than the adult rat. FB(1) treatment produces in the forebrain and brainstem: (i) an increase in SA levels and SA/SO ratio, (ii) a reduction in myelin deposition, and (iii) an impairment of 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) activity. FB(1) effects on myelin are similar to those produced by starvation (temporary removal of pups from dam during postnatal period), thus suggesting that hypomyelination could be due, at least partly, to a nutritional deficiency. Finally, FB(1) reduces the uptake of folate in different cell lines. The resulting folate deficiency could explain the association of FB(1) exposure with neural tube defects.
Asunto(s)
Encéfalo/efectos de los fármacos , Fumonisinas/toxicidad , Esfingosina/análogos & derivados , Animales , Encéfalo/enzimología , Encéfalo/metabolismo , Dieta , Deficiencia de Ácido Fólico/inducido químicamente , Deficiencia de Ácido Fólico/fisiopatología , Fumonisinas/administración & dosificación , Masculino , Oxidorreductasas/antagonistas & inhibidores , Ratas , Esfingosina/metabolismoRESUMEN
Prenatal exposure to low concentrations of carbon monoxide (CO, 150 ppm) causes long-term alterations in sphingomyelin (SM) homeostasis in peripheral nervous system, but not brain of male rat offspring. In particular, unlike sphinganine (intermediate of complex sphingolipid biosynthesis de novo), the concentrations of sphingosine (intermediate of complex sphingolipid turnover) were increased by 2.35-fold in the sciatic nerve of CO-exposed offspring with respect to controls (P<0.05, overall one-way ANOVA). These subtle alterations were not accompanied by changes in motor activity (F=0.25, df=1/10, n.s., overall one-way-ANOVA). The results suggest that the SM homeostasis in the sciatic nerve is particularly susceptible to prenatal CO exposure resulting in maternal carboxyhaemoglobin (HbCO) levels equivalent to those found in human cigarette smokers.