EFFECTS OF INTRAUTERINE AND POSTNATAL PROTEIN-CALORIE MALNUTRITION ON METABOLIC ADAPTATIONS TO EXERCISE IN YOUNG-RATS

The effect of intrauterine and postnatal protein-calorie malnutrition on the biochemical ability to perform exercise was investigated in young male rats. Malnourished rats were obtained by feeding dams a low-protein (6%) casein-based diet prepared in the laboratory during pregnancy and lactation. Control rats received an isocaloric diet containing 25% protein. The low-protein diet contained additional starch and glucose. At 45 days of age, malnourished rats showed lower body weight, serum protein, albumin and glucose levels, hematocrit values and heart glycogen content but higher circulating free fatty acids and gastrocnemius muscle glycogen than control rats. In response to exercise (50 min of swimming), control rats displayed lower heart, gastrocnemius and liver glycogen levels whereas malnourished rats showed low glycogen levels only in the gastrocnemius muscle. Both control and malnourished rats showed high serum glucose and free fatty acid levels after exercise. In conclusion, protein-calorie malnutrition improved muscle glycogen storage but this substrate was broken down to a greater extent in response to exercise. Malnourished rats were able to perform exercise maintaining high blood glucose levels, as observed in control rats, perhaps as a consequence of the elevated availability of circulating free fatty acids.

Developmental and behavioral effects of postnatal amitraz exposure in rats

The effects of postnatal amitraz exposure on physical and behavioral parameters were studied in Wistar rats, whose lactating dams received the pesticide (10 mg/Kg) orally on days 1, 4, 7, 10, 13, 16 and 19 of lactation; control dams received distilled water (1 ml/kg) on the same days. A total of 18 different litters (9 of them control and 9 experimental) born after a 21- day gestation were used. The results showed that the median effective time (ET50) for fur development, eye opening, testis descent and onset of the startle response were increased in rats postnatally exposed to amitraz (2.7, 15.1, 21.6 and 15.3 days, respectively) compared to those of the control pups (1.8, 14.0, 19.9 and 12.9 days, respectively). The ages of incisor eruption, total unfolding of the external ears, vaginal and ear opening and the time taken to perform the grasping hindlimb reflex were not affected by amitraz exposure. Pups from dams treated with amitraz during lactation took more time (in seconds) to perform the surface righting reflex on postnatal days (PND) 3 (25.0 ±2.0), 4 (12.3 ± 1.2) and 5 (8.7 ± 0.9) in relation to controls (10.6 ± 1.2; 4.5 ± 0.6 and 3.4 ± 0.4, respectively); the climbing response was not changed by amitraz. Postnatal amitraz exposure increased spontaneous motor activity of male and female pups in the open-field on PND 16 (140± 11)and 17(124± 12), and 16 (104±9), 17 (137 ± 9) and 18 (106 ± 8), respectively. Data on spontaneous motor activity of the control male and female pups were 59 ± 11 and 69 ± 10 for days 16 and 17 and 49 ± 9, 48 ± 7 and 56 ± 7 for days 16, 17 and 18, respectively. Some qualitative differences were also observed in spontaneous motor behavior; thus, raising the head, shoulder and pelvis matured one or two days later in the amitraz- treated offspring. Postnatal amitraz exposure did not change locomotion and rearing frequencies or immobility time in the open-field on PND 30, 60 and 90. The present findings indicate that postnatal exposure to amitraz caused transient developmental and behavioral changes in the exposed offspring and suggest that further investigation of the potential health risk of amitraz exposure to developing human and animal offsprings may be warranted.

Morphometric study of the postnatal growth of the parotid gland of the mouse

The growth of the mouse parotid glands during 7 and 35 days of postnatal life was studied by morphometric methods. The mass of the gland, the volume of each morphological compartment, and the cell number in each compartment were evaluated. The data obtained for each evaluated dimension were adjusted by an exponential equation, of the type Y = a.e KX, thus permitting the calculation of their mean duplication time (T D), i.e., an estimation of their growth rate. Analysis of the results showed a marked 1,424% increase in the gland mass during the whole studied period, with T D = 7.10 days. This growth occurred by increases in absolute volume of acini, intercalated ducts, striated ducts, excretory ducts and stroma, with percentual increases of 3,048%, 417%, 2,662%, 2,594% and 367%, respectively, and T Ds of 5.62, 11.71, 5.55, 5.47 and 14.45 days, respectively. Analysis of the cell number growth in each compartment showed increases of 1,904%, 285%, 1,228%, 1,090% and 286%, respectively, and T Ds of 6.62, 20.40, 7.19, 7.26 and 14.51 days, respectively. Based on the present results, we concluded that the growth of the mouse parotid glands from day 7 to day 35 of age occurred by intense cell accumulation, mainly in the acini, striated ducts and excretory ducts, with a growth rate sensibly higher than that of the intercalated ducts and stroma.

Maternal obesity disturbs the postnatal development of gonocytes in the rat without impairment of testis structure at prepubertal age

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Muscle glycogen metabolism changes in rats fed early postnatal a fructose-rich diet after maternal protein malnutrition: effects of acute physical exercise at the maximal lactate steady-state intensity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Loss of nuclear poly(A)-binding protein 1 (PABPN1) causes defects in myogenesis and mRNA biogenesis

The nuclear poly(A)-binding protein 1 (PABPN1) is a ubiquitously expressed protein that plays a critical role in polyadenylation. Short expansions of the polyalanine tract in the N-terminus of PABPN1 lead to oculopharyngeal muscular dystrophy (OPMD), which is an adult onset disease characterized by eyelid drooping, difficulty in swallowing and weakness in the proximal limb muscles. Although significant data from in vitro biochemical assays define the function of PABPN1 in control of poly(A) tail length, little is known about the role of PABPN1 in mammalian cells. To assess the function of PABPN1 in mammalian cells and specifically in cells affected in OPMD, we examined the effects of PABPN1 depletion using siRNA in primary mouse myoblasts from extraocular, pharyngeal and limb muscles. PABPN1 knockdown significantly decreased cell proliferation and myoblast differentiation during myogenesis in vitro. At the molecular level, PABPN1 depletion in myoblasts led to a shortening of mRNA poly(A) tails, demonstrating the cellular function of PABPN1 in polyadenylation control in a mammalian cell. In addition, PABPN1 depletion caused nuclear accumulation of poly(A) RNA, revealing that PABPN1 is required for proper poly(A) RNA export from the nucleus. Together, these experiments demonstrate that PABPN1 plays an essential role in myoblast proliferation and differentiation, suggesting that it is required for muscle regeneration and maintenance in vivo.

High sodium intake during postnatal phases induces an increase in arterial blood pressure in adult rats

Coordenadoria de Aperfeiçoamento em Pesquisa (CAPES)

Análise histométrica do desenvolvimento testicular de cutias (Dasyprocta aguti) criadas em cativeiros

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

The locus coeruleus and central chemosensitivity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Matemal separation affects cocaine-induced locomotion and response to novelty in adolescent, but not in adult rats

Maternal separation is known to exert long-term effects on both behavior and the neuroendocrine system. We investigated cocaine-induced locomotor activation as well as the locomotor and corticosterone response to forced novelty in maternally separated adolescent and adult rats. Maternal separation consisted of separating litters from their darns daily during 5 h from postnatal days 2 to 6. Control animals were subjected only to regular cage changes. Cocaine- (10 mg/kg, i.p.) and novelty-induced locomotion were recorded in an activity cage. After the animals were tested for behavioral response to novelty, trunk blood samples were collected and plasma corticosterone levels were determined by radioimmunoassay. Adolescent rats exposed to maternal separation exhibited an increased locomotor response to novelty and cocaine; corticosterone levels were lower in these adolescent animals, after exposure to the novel environment. These effects of materrial separation were not observed in rats that were tested as adults. Thus the maternal separation protocol produced enduring but transient changes in the behavioral response to cocaine and in the stress response to novelty. (C) 2004 Elsevier B.V. All rights reserved.

Exposure to chronic stress increases the locomotor response to cocaine and the basal levels of corticosterone in adolescent rats

Repeated exposure to stress results in augmentation in the locomotor response to psychostimulant drugs. We investigated the locomotor response to a novel environment or cocaine [ 10 mg/kg, intraperitoneally (i.p.)] and basal corticosterone levels in male adolescent rats exposed to chronic restraint or variable stress. Animals in the chronic restraint group were restrained for 1 hour daily. The chronic variable stress protocol consisted of exposure to different stressors twice a day in random order. Chronic restraint and variable stress regimens began simultaneously on postnatal day (P) 25 and were applied for 10 days. During this period the control group was left undisturbed except for cleaning the cages. Three days after the last exposure to stress, cocaine- and novelty-induced locomotion were recorded in an activity cage. Plasma corticosterone levels were determined in a subset of stress and control animals. Exposure to both chronic restraint and variable stress increased cocaine- induced locomotion and basal corticosterone plasma levels, while no change was observed in the response to a novel environment. Moreover, rats exposed to variable stress displayed the greatest locomotor response following a challenge dose with cocaine when compared to control and chronic restraint stress groups. This observation indicates that the stress regimen is relevant to the degree of stress-induced sensitization to cocaine.

Exposição repetida à cafeína aumenta a atividade locomotora induzida pelo femproporex em ratos adolescentes e adultos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Repeated exposure of adolescent rats to oral methylphenidate does not induce behavioral sensitization or cross-sensitization to nicotine

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Effect of cocaine on periadolescent rats with or without early maternal separation

Cocaine-induced behavioral sensitization and weight loss were investigated in periadolescent Wistar rats kept with their mothers or subjected to repeated maternal separation. Litters allocated to the separation procedure were placed in a temperature-controlled (33ºC) chamber for 3 h per day from postnatal day 6 (P6) to P20. Non-handled rats were left undisturbed until weaning. Treatments were started on P30-31 and the test was performed on P36-37. Animals received injections of saline or cocaine (10 mg/kg, sc) twice daily for 5 days. on day 6 all animals received saline. on day 7 animals were challenged with 10 mg/kg cocaine and their locomotion was evaluated in activity cages. A third group received saline throughout the 7-day period. Body weights were recorded on P30-31 and P36-37. Two-way ANOVA on body weights showed a main effect of treatment group (F(1,35) = 10.446, P = 0.003; N = 10-12). Non-handled rats treated with cocaine for 5 days gained significantly less weight, while no significant effect was observed in maternally separated rats. Two-way ANOVA revealed a main effect of drug treatment on locomotor activity (F(2,32) = 15.209, P<0.001; N = 6-8), but not on rearing condition (F(1,32)<0.001, P = 0.998). Animals pretreated with cocaine showed a clear behavioral sensitization relative to the saline group. No difference in the magnitude of sensitization was found between separated and non-handled animals. Only the effect of cocaine on weight gain was significantly affected by repeated episodes of early maternal separation during the pre-weaning period.