Effects of deltamethrin on granule cell migration during postnatal development of rat cerebellum

Deltamethrin (DLT; 0.7mg/kg/body wt/day, i.p., dissolved in propylene glycol) administration during postnatal days 913 in Albino rat pups, resulted in a delayed appearance of radial glial fibers, that guide the migration of granule cells. Moreover, the radial glial fibers in the DLT-treated pups were disorganized, hypertrophied and heavily stained. Thus, it is being proposed that although after exposure to DLT the neuronal proliferation occurs at normal rate, the neuronal migration along the stumpy and crumpled radial fibers hamper the journey of the healthy neurons to their proper destination.     

The effect of late prenatal and/or early postnatal zinc deficiency on the development and some biochemical aspects of the cerebellum and hippocampus in rats

In rats, late prenatal and/or early postnatal zinc deficiency results in behavioural anomalies in adult animals, but not in overt dysmorphogenesis of the central nervous system. Cerebellar and hippocampal development occurs mainly in the first three weeks postnatally and zinc accumulates specifically in the mossy fibres of the hippocampus during this period.In the present investigation, rat pups were suckled by dams fed a zinc-deficient (<0.5 mg/kg) diet either from day 19 of pregnancy or from parturition. Control animals were restricted-fed the same diet supplemented with 100 mg zinc/kg. Studies were performed on pups either on day 18 postpartum in the case of animals fed the experimental diets from parturition, or on day 20 for pups which received treatment from day 19 of gestation.Cerebellar and hippocampal weights were lower in pups suckling from zinc-deficient dams but zinc levels were not affected in either organ, although histological evidence suggested less zinc in the hippocampal mossy fibres. Incorporation of H-thymidine into cerebellar and hippocampal DNA was not affected by maternal zinc status, nor was the activity of the zinc metalloenzyme alkaline phosphatase.The activity of the myelin-marker enzyme 2′, 3′-cyclic nucleotide 3′-phosphohydrolase was substantially lower in both regions of the brain in zinc deprived pups, especially in the hippocampus. Activity of the zinc metalloenzyme L-glutamic acid dehydrogenase was also diminished in both tissues from 20-day-old pups and in the hippocampi of 18-day-old animals.The data suggest that cerebellar and hippocampal DNA synthesis is not seriously affected by late prenatal and/or early postnatal zinc depletion, but that the activities of two enzymes associated with neural function are. The possibility is raised that these defects may be associated with the behavioural changes observed in rats subjected to zinc impoverishment during the period of maximal cerebellar and the hippocampal development.     

Evaluation of Reproductive Disorders in Female Rats Exposed to N‐Methyl‐2‐Pyrrolidone

BACKGROUND: N‐methyl‐2‐pyrrolidone (NMP) is a solvent used in the petrochemical, and electronic industries, in pesticides production, veterinary drugs, and paint removers. The aim of study was to evaluate the relationship between the dose of NMP given orally and its effect on fertility in female rats and early development of their progeny. METHODS: Females were exposed by gavage 5 days/week to NMP at 150, 450, or 1000 mg/kg/day 2 weeks before mating, during mating, gestation, and lactation. On the first postnatal day (PND 1), the live and dead pups were counted, weighed, and gender was determined. On PND 4, the litters were culled to eight animals each and balanced for gender. Young animals were observed during 3 weeks after birth. RESULTS AND CONCLUSION: Fertility index did not significantly differ in the control and the group exposed at 150 mg/kg/day but it was significantly lower in the groups exposed at 450 or 1000 mg/kg/day. The number of live pups in the group exposed to the highest dose was significantly lower and the number of stillbirths in litters was significantly greater. Survival of the pups from all exposed groups during the 3 weeks after birth was significantly lower than the control animals. The results of our study indicate that intragastric exposure of female rats to NMP before pregnancy during gestation causes significant impairment in female fertility and intrauterine mortality rates. At lower doses, toxic or slightly toxic to the mothers, this substance causes decrease in viability and physical development of progeny.     

Maternal entrainment of tau mutant hamsters.

Maternal entrainment of the circadian wheel-running activity rhythm was examined in Syrian hamsters heterozygous for a single gene mutation (tau) that affects the free-running period of circadian rhythms. Heterozygous tau pups were born to and raised by wild-type mothers under constant dim light. The pups' wheel-running activity was recorded after weaning on postnatal day 18 or 24. Pups weaned on day 18 had an average free-running period of 21.70 hr, demonstrating that the tau phenotype was fully expressed at this age. Using the activity onset of the postnatal free-running rhythms as a phase reference, we estimated the phase relationships between the pups and their mothers on days 18 and 24. In contrast to results with wild-type pups, the activity rhythms of tau pups were not in phase with the rhythms of their wild-type mothers; that is, activity onsets of mothers and pups did not coincide. The pups did, however, show synchrony among themselves, indicating that they had been exposed to a synchronizing signal sometime during development. It is likely that this synchronizing signal was provided by the mothers, since pups from different litters showed phase relationships similar to those of their mothers. Thus the mothers provided a signal that was sufficient to cause entrainment, despite the 2-hr difference in free-running period between the mothers and pups. Although the pups' activity rhythms appeared to have been entrained by the mothers, they were clearly free-running by postnatal day 18. The mechanism for entrainment is lost during the course of development, despite continued interaction between the mothers and pups.     

In utero and early-life exposure of rats to a Wi-Fi signal: screening of immune markers in sera and gestational outcome

An experimental approach was used to assess immunological biomarkers in the sera of young rats exposed in utero and postnatal to non-ionizing radiofrequency fields. Pregnant rats were exposed free-running, 2 h/day and 5 days/week to a 2.45 GHz Wi-Fi signal in a reverberation chamber at whole-body specific absorption rates (SAR) of 0, 0.08, 0.4, and 4 W/kg (with 10, 10, 12, and 9 rats, respectively), while cage control rats were kept in the animal facility (11 rats). Dams were exposed from days 6 to 21 of gestation and then three newborns per litter were further exposed from birth to day 35 postnatal. On day 35 after birth, all pups were sacrificed and sera collected. The screening of sera for antibodies directed against 15 different antigens related to damage and/or pathological markers was conducted using enzyme-linked immunosorbent assay (ELISA). No change in humoral response of young pups was observed, regardless of the types of biomarker and SAR levels. This study also provided some data on gestational outcome following in utero exposure to Wi-Fi signals. Mass evaluation of dams and pups and the number of pups per litter was monitored, and the genital tracts of young rats were observed for abnormalities by measuring anogenital distance. Under these experimental conditions, our observations suggest a lack of adverse effects of Wi-Fi exposure on delivery and general condition of the animals.     

Effects of cobalt on postnatal development and late gestation in rats upon oral administration

Four groups of pregnant Wistar rats, each of which consisted of 15 animals were administered 0, 12, 14 and 48 mg/kg/day of cobalt (II) chloride from the 14th day of gestation through 21 days of lactation. The offspring were observed for mortality, body weight, body and tail length and general symptomatology after 1, 4 and 21 days of nursing. The number of litters was higher for the control group. The survival ratios were also higher for the control group. Besides, a dose-dependent delay in the growth of the living young could be observed. No significant differences in organ weights in the animals killed 21 days after birth were observed. The blood parameters analysed did not show differences between the treated and control pups. Cobalt produced toxic effects on the mothers, affecting the late gestation as well as the postnatal development of the pups.     

Comparative Effects of Ethanol and Malnutrition on the Development of Catecholamine Neurons: Changes in Neurotransmitter Levels

Abstract: The comparative effects of exposure to ethanol and malnutrition on the concentrations of tyrosine and catecholamines in whole brain and selected regions of brain have been studied in the developing rat. These animals were the offspring of optimally nourished rats (control pups), of rats fed a diet with 35% of the calories supplied by ethanol (ETOH pups), or of animals fed a diet calorically equivalent to the latter but lacking ethanol (iso-caloric, 1C pups). These diets were administered to dams either during the last week of gestation (prenatal) or during lactation (postnatal). Tyrosine levels were elevated prior to birth in the prenatal ETOH or IC pups or at 1 and 2 weeks of age in postnatal ETOH or 1C pups as compared with values found in the control offspring. Dopamine concentration in whole brain was significantly lower in prenatal ETOH pups than in prenatal IC pups at 3 weeks of age. Levels in the brains of postnatal ETOH pups were lower than control values, but not relative to animals exposed to 1C diet. Investigation of corpus striatum showed a significant decrease in dopamine concentration compared with control or IC pup values as a result of postnatal exposure to ethanol. Norepinephrine levels in the whole brain of prenatal ETOH pups were consistently 30–40% lower than either control or matched 1C pups during development. At 3 weeks of age, the norepinephrine levels in the hypothalamus of animals exposed to ethanol pre or postnatally were 30–60% lower than values in the corresponding region in either control or 1C pups. In the rat model described, ethanol caused a decrease in catecholamine levels, perhaps solely by affecting the norepinephrine neurons.     

Effect of prenatal nicotine exposure on biphasic hypoxic ventilatory response and protein kinase C expression in caudal brain stem of developing rats.

Current evidence suggests that maternal smoking is associated with decreased respiratory drive and blunted hypoxic ventilatory response (HVR) in the newborn. The effect of prenatal nicotine exposure on overall changes in HVR has been studied; however, there is limited data on the effect of nicotine exposure on each component of biphasic HVR. To examine this issue, 5-day timed-pregnant Sprague-Dawley rats underwent surgical implantation of an osmotic minipump containing either normal saline (Con) or a solution of nicotine tartrate (Nic) to continuously deliver free nicotine at 6 mg.kg of maternal weight(-1).day(-1). Rat pups at postnatal days 5, 10, 15, and 20 underwent hypoxic challenges with 10% O(2) for 20 min using whole body plethysmography. At postnatal day 5, Nic was associated with attenuation of peak HVR; peak minute ventilaton increased 44.0 +/- 6.8% (SE) from baseline in Nic pups, whereas that of Con pups increased 62.9 +/- 5.1% (P < 0.05). Nic pups also had a reduction in the magnitude of ventilatory roll-off; minute ventilation at 15 min decreased 7.3 +/- 7.1% in Nic pups compared with 27.3 +/- 4.0% in Con pups (P < 0.05). No significant difference in HVR was noted at postnatal days 10, 15, and 20. Hypercapnic response was similar at all ages. We further investigated the effect of prenatal nicotine exposure on PKC expression in the caudal brain stem (CB) of developing rats. At postnatal day 5, Nic was associated with increased expression of PKC-beta and PKC-delta in CB, whereas other PKC isoforms were not affected. It is concluded that prenatal nicotine exposure is associated with modulation of biphasic HVR and a selective increase in the expression of PKC-beta and PKC-delta within the CB of developing rats.     

Postnatal dexamethasone and long term learning and memory functions in developing rats: Effect of postnatal age and gender

In this study, we investigated the effect of dexamethasone on the long-term learning and memory functions in developing rats. In Sprague-Dawley rat pups, we administered a daily dose of dexamethasone (0.5 mg/kg/day) for three consecutive days in three groups of animals: the "ultra-early" group received steroids on postnatal days (PND) 1-3; the "early" group received the drug on PNDs 8-10, and the "late" group received the drug on PNDs 28-30. The control group was not given any medication. All animals underwent structured CNS examinations beginning on PND 15, and continued through PND 20. The pups were tested for spatial learning and memory functions using the Morris Water Maze (MWM) on PNDs 31 through 35, 45 through 49, and 59 through 63. They were also tested for reward-based learning and memory functions using Radial Arm Maze (RAM) on PNDs 70 through 72. We analyzed the effect of dexamethasone, postnatal age, and sex on neurological milestones, and learning and memory functions. We found that neurological examination findings were similar in all groups, as were the results of the reward-based learning using RAM. However, in the MWM, the total distance of swimming and the total time to find the hidden platform showed considerable difference among the groups. Although these functions improved with postnatal age, the female pups in all three steroid groups, and the male pups in the late-steroid group lagged significantly in learning and memory functions compared to the controls, and such lags were transient. However, the interaction terms between dexamethasone, age, and sex were also significant in MWM test results. Steroids administered postnatally may have transient, retarding effect on learning and memory functions, and that animal age and sex may modify such effects. Such lags are not global, but specific to the types of memory tests used, implicating different neural circuitries in the pathogenesis of such abnormalities. Although transient, if such adverse effects occur at critical phases during brain maturation, the implications for poor, long-term outcomes may be more significant. The mechanisms underlying such changes need to be explored.     

Oxygen consumption and survival prediction in neonatal rats exposed to prenatal hypervitaminosis A

Fetal exposure to excess vitamin A results in a highly variable degree of lung pathology and high neonatal mortality in the Long-Evans rat. The present study evaluated O2 consumption in newborn of vitamin A-treated, vehicle-treated, and untreated pregnancies on five consecutive postnatal days beginning with the day of delivery (D0). Pregnant female rats were treated by gavage with 160,000 USP units of retinyl acetate dissolved in 0.5 ml corn oil on days 15 through 19 of gestation. Vehicle and undisturbed controls were run concurrently. All animals delivered spontaneously, and the pups were tattooed and individually tested in a closed system consisting of three chambers submerged within a thermostatically controlled water bath at 33 degrees C. Vitamin A-exposed pups, as a group, have significantly lower QO2 (ml O2 consumed/min/kg body weight) values than controls through postnatal day 2 (p less than 0.05). By days 3 and 4 of age, the mean QO2 values of surviving vitamin A-treated pups were similar to those of controls. A QO2 of 30 or greater on day 0 appears to be critical for early neonatal survival of vitamin A-exposed pups, as 87% of the pups with initial QO2 less than 30 died prior to day 4. Oxygen consumption rates in teratogen-exposed pups exhibiting low QO2 on day 0 rarely reached normal levels. In contrast, the occasional control pup with such low initial levels were well within normal limits (means +/- 1 SD) by the following day.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of the developmental effects on mice after prenatal, or pre- and postnatal exposure to 2,3-dimercaptopropane-1-sulfonic acid (DMPS)

The sodium salt of 2,3-dimercaptopropane-1-sulfonic acid (DMPS), a water soluble metal complexing agent, was administered to four groups of pregnant Swiss mice at 0, 70, 210, and 630 mg/kg/day by two dosing schedules: gestation day 14 until birth (prenatal exposure), and gestation day 14 until postnatal day 21 (pre- and postnatal section). Dams were allowed to deliver and the number of live and dead pups recorded. Each pup was sexed and weighed on days 0, 4, 14, and 21. Also, pinna detachment, incisor eruption and eye opening were monitored. No adverse effects on offspring survival or development were evident in either exposures at doses employed in this study. The "no observable effect level" (NOEL) for health hazard to the developing fetus or pup was 630 mg DMPS/kg/day. This dose is much higher than the amounts of DMPS usually administered in human heavy metal poisoning.     

Neonatal maternal separation enhances phrenic responses to hypoxia and carotid sinus nerve stimulation in the adult anesthetized rat.

In awake animals, our laboratory recently showed that the hypoxic ventilatory response of adult male (but not female) rats previously subjected to neonatal maternal separation (NMS) is 25% greater than controls (Genest SE, Gulemetova R, Laforest S, Drolet G, and Kinkead R. J Physiol 554: 543-557, 2004). To begin mechanistic investigations of the effects of this neonatal stress on respiratory control development, we tested the hypothesis that, in male rats, NMS enhances central integration of carotid body chemoafferent signals. Experiments were performed on two groups of adult male rats. Pups subjected to NMS were placed in a temperature-controlled incubator 3 h/day from postnatal day 3 to postnatal day 12. Control pups were undisturbed. At adulthood (8-10 wk), rats were anesthetized (urethane; 1.6 g/kg), paralyzed, and ventilated with a hyperoxic gas mixture [inspired O2 fraction (Fi(O2)) = 0.5], and phrenic nerve activity was recorded. The first series of experiments aimed to demonstrate that NMS-related enhancement of the inspiratory motor output (phrenic) response to hypoxia occurs in anesthetized animals also. In this series, rats were exposed to moderate, followed by severe, isocapnic hypoxia (Fi(O2) = 0.12 and 0.08, respectively, 5 min each). NMS enhanced both the frequency and amplitude components of the phrenic response to hypoxia relative to controls, thereby validating the use of this approach. In a second series of experiments, NMS increased the amplitude (but not the frequency) response to unilateral carotid sinus nerve stimulation (stimulation frequency range: 0.5-33 Hz). We conclude that enhancement of central integration of carotid body afferent signal contributes to the larger hypoxic ventilatory response observed in NMS rats.     

Development of social vocalizations in mice

Adult mice are highly vocal animals, with both males and females vocalizing in same sex and cross sex social encounters. Mouse pups are also highly vocal, producing isolation vocalizations when they are cold or removed from the nest. This study examined patterns in the development of pup isolation vocalizations, and compared these to adult vocalizations. In three litters of CBA/CaJ mice, we recorded isolation vocalizations at ages postnatal day 5 (p5), p7, p9, p11, and p13. Adult vocalizations were obtained in a variety of social situations. Altogether, 28,384 discrete vocal signals were recorded using high-frequency-sensitive equipment and analyzed for syllable type, spectral and temporal features, and the temporal sequencing within bouts. We found that pups produced all but one of the 11 syllable types recorded from adults. The proportions of syllable types changed developmentally, but even the youngest pups produced complex syllables with frequency-time variations. When all syllable types were pooled together for analysis, changes in the peak frequency or the duration of syllables were small, although significant, from p5 through p13. However, individual syllable types showed different, large patterns of change over development, requiring analysis of each syllable type separately. Most adult syllables were substantially lower in frequency and shorter in duration. As pups aged, the complexity of vocal bouts increased, with a greater tendency to switch between syllable types. Vocal bouts from older animals, p13 and adult, had significantly more sequential structure than those from younger mice. Overall, these results demonstrate substantial changes in social vocalizations with age. Future studies are required to identify whether these changes result from developmental processes affecting the vocal tract or control of vocalization, or from vocal learning. To provide a tool for further research, we developed a MATLAB program that generates bouts of vocalizations that correspond to mice of different ages.     

The postnatal maternal environment affects autoimmune disease susceptibility in A/J mice

The postnatal maternal environment is known to increase susceptibility to a number of autoimmune diseases. Here we asked whether the postnatal maternal environment could influence autoimmune disease development to day 3 thymectomy (d3tx)-induced autoimmune ovarian disease (AOD) and experimental allergic encephalomyelitis (EAE) in cross-fostered A/J and B6 mice. A/J pups foster-nursed by B6 mothers exhibit an increase in autoimmune disease development while cross-fostering B6 pups on A/J mothers did not alter their susceptibility. The increase in AOD incidence seen in foster-nursed d3tx A/J mice correlated with a decrease in the total number of CD4⁺ T cells in the lymph nodes of these animals. Analysis of the cellular composition in the milk revealed that B6 mice shed significantly more maternally derived lymphocytes into their milk compared to A/J mothers. These data suggest that there are maternally derived postnatal factors that influence the development of autoimmune disease in A/J mice.     

The chemosensory support of feeding behavior in precocial and altricial mammals during ontogeny]

The development of the structure and function of chemosensory apparatus of the tongue of mature and immature mammals was studied by scanning electron microscopy and in behavioral tests. Heterochronic development of receptors structures of dorsal surface of the tongue was established. At birth the chemoreceptors of body and root of the tongue were relatively mature in morphological aspects (the number of taste buds with pore). Taste pores in buds of anterior part of the tongue were found immediately at birth in mature and at the third week of postnatal period in immature animals. Behavioral tests found functional immaturity of chemosensory structures. Immature pups were able to recognize flavoured solutions only on the 7-10 day of age, and preference-aversion reactions of mature pups appeared to the third day of age. The data obtained are discussed in the respect of different ways of adaptation to food contacts with environment of the pups of mature and immature animals.     

Early life stress increases anxiety-like behavior in Balbc mice despite a compensatory increase in levels of postnatal maternal care

A better understanding of the molecular and cellular mechanisms by which early life stress (ELS) modifies brain development and adult behavior is necessary for diagnosing and treating psychopathology associated with exposure to ELS. For historical reasons, most of the work in rodents has been done in rats and attempts to establish robust and reproducible paradigms in the mouse have proven to be challenging. Here we show that under normal rearing conditions, increased levels of postnatal maternal care are associated with a decrease in anxiety-like behavior in BALB/cByj offspring. Brief daily pup-dam separation (BDS) during the postnatal period was associated with increased postnatal maternal care but was surprisingly associated with increased anxiety-like behavior in adult offspring, providing the first example in which offspring receiving higher levels of postnatal maternal care are more anxious in adulthood. Plasma corticosterone levels were elevated in BDS pups even 3 h after the pups were reunited with the dam, suggesting that this paradigm represents a form of early life stress. We also show that levels of total RNA and DNA in the hippocampus reach a peak at postnatal day 14 and that exposure to BDS seems to inhibit this developmental growth spurt. We propose that exposure to stress during the postnatal period overrides the ability of high levels of postnatal maternal care to program anxiety-like behavior by inhibiting the normal growth spurt that characterizes this period.     

Thyroid dependent maturation of β-adrenergic receptors in the rat lung

β-Adrenergic receptors were identified in membranes of fetal and postnatal rat lung with (?)-[³H]dihydroalprenolol, [³H]DHA. β-Receptor number (Bmax) increased 11-fold from day 18 of gestation to adult levels by day 28 of postnatal life. The increase of β-adrenergic receptors occurring between postnatal days 15 and 28 was dependent on thyroxine (T4) in propylthiouracil treated pups. β-Adrenergic receptors on day 28 were identical in euthyroid (PTU + T4) as compared to normal control pups (489±31 and 491±30 femtomoles·mg^?1) however receptors were markedly reduced in 28 day hypothyroid pups (PTU alone), Bmax = 294±21.5, m±S.E. p<0.01. Treatment of the hypothyroid pups with T4 for three days on postnatal day 25 increased β-adrenergic receptors approximately two-fold by day 28. This thyroid hormone dependent increase in lung β-adrenergic receptors occurs between postnatal days 15 and 28 coincident with the known increase in thyroid gland activity in the rat pup.     

The effect of the limitation of afferent inflow in early ontogeny on the evoked activity of projective neurons depends on the degree of the maturity of the sensory inputs]

The study is focused on the influence of a partial limitation of the sensory inflow in rat pups on the development of the sensory systems, which mature earlier and later. In accordance with the ontogenetic rule of proximal-distal maturation, the sensory inflow from the forelimbs matures faster than that from the hindlimbs. Fourteen Wistar rat pups (from 28) were deafferented on the 13th day of postnatal ontogeny (a small portion of the median nerve was unilaterally dissected). The background and evoked activity of single neurons was recorded in 26-47-day-old pups in the somatosensory cortex (in the projection areas of the intact n. medianus, which matures earlier, and n. ischiadicus, which matures later). The changes in firing activity produced by deafferentation were observed. In the projection area of the intact forelimb of the denervated rats, the incidence of inhibitory responses significantly increased, whereas the incidence of completes responses significantly decreased. In the hindlimb projection area of the denervated animals the background firing rate was significantly lower and the incidence of activation responses was increased.     

Effects of oral meso-2,3-dimercaptosuccinic acid (DMSA) administration on late gestation and postnatal development in the mouse

The present study was conducted to evaluate the effects of meso-2,3-dimercaptosuccinic acid (DMSA) on late gestation and postnatal viability and growth in the mouse. DMSA was given po to four groups of pregnant Swiss mice at 0, 200, 400, and 800 mg/kg/day from day 14 of pregnancy until postnatal day 21. At birth, the following data were recorded: length of gestation, number of live, dead, and abnormal pups, sex, and individual pup weights. Each pup was weighed again on day 4, 14, and 21 of lactation. Pinna detachment, incisor eruption and eye opening were also monitored. No treatment-related signs of toxicity were noted in any of the dams during the study. No adverse effects on offspring survival or development were evident in the 200 or 400 mg DMSA/kg/day groups. However, on days 14 and 21 of lactation a significant decrease in pup body weight was observed in the 800 mg/kg/day group. Also, a significant increase in the relative weight of the brain was seen in this group. The "no observable effect level" (NOEL) for health hazards to the developing pup was greater than 400 mg/kg/day. This dose is higher than the amounts of DMSA usually given in the treatment of human heavy metal intoxications.