Early Postnatal Days Research Articles

Role of Cord Blood Albumin and Bilirubin for Prediction of Significant Neonatal Jaundice

Introduction: Nearly 60-80% of the term and preterm neonates are affected due to rise in bilirubin levels during early postnatal days, and causes readmission of the neonate sometimes with severe jaundice, which can be reduced if neonatal hyperbilirubinemia can be predicted early. The study was conducted to evaluate the predictive values of cord blood albumin and bilirubin for neonatal hyperbilirubinemia and to evaluate the better predictor between them. Method: In this hospital based observational study, 152 healthy term newborns with birth weight more than 2.5 kg were included. Assessment of cord blood haemoglobin, blood group, albumin and bilirubin levels was done. Follow-up for first consecutive five days after birth was done and assessed daily to look for evidence of jaundice, sepsis or any other illness. Serum bilirubin was evaluated at 72-96 hours of life in all neonates and was done early, if clinically indicated. Receiver’s Operating Characteristics curves were used for calculating the cut-off values of cord blood albumin and bilirubin in relation to hyperbilirubinemia. Result: The cut-off values obtained for albumin and bilirubin of cord blood was < 2.56 mg/dL and >2.33 mg/dL respectively at optimum sensitivity and specificity. Cord blood bilirubin was found to be highly sensitive for early recognition of significant neonatal hyperbilirubinemia as compared to cord blood albumin and can be used for screening purpose. Conclusion: Cord blood albumin and bilirubin can be used for negating the development of NNHB, but for screening purpose, cord blood bilirubin is more predictive of neonatal hyperbilirubinemia.

The effects of early weaning on Pavlovian fear conditioning in young rats.

Early life stress enhances memory for Pavlovian fear conditioning. Stress enhancements on fear conditioning following early weaning, however, have yet to be studied in periweaning rats. Early weaning is a relevant animal model for human early life trauma, and Pavlovian fear conditioning is useful for identifying links between stress-induced developmental changes and behavior. We hypothesized that early weaning-on postnatal day (P)15-would lead to higher levels of conditional freezing relative to rats weaned later in life. Periweaning rats were trained with a discrete conditional stimulus (CS) and a shock unconditional stimulus (US), and tested 1 or 15 days later. Enhanced retention was observed in early weaned rats receiving forward paired CS-US training in Experiment 1, though this did not replicate in the second experiment. Despite overall enhancements in early weaned rats in Experiment 1, infantile amnesia effects were not overcome in young rats tested 15 days after training. Enhanced freezing levels in early weaned rats were not observed in subjects receiving unpaired CS, US training, and sensitivity to the US was not different due to age at weaning. Potential mechanisms underlying weaning-related enhancements and considerations for future studies including the role of social transmission of fear information are discussed.

Cell Type-specific Knockout with Gli1-mediated Cre Recombination in the Developing Cerebellum.

The inducible Cre-loxP system provides a useful tool for inducing the selective deletion of genes that are essential for proper development and enables the study of gene functions in properly developed animals. Here, we show that inducible Cre-loxP driven by the Gli1-promoter can induce cell-type-specific deletion of target genes in cerebellar cortical neurons. We used reporter mice containing the YFP (yellow fluorescence protein) gene at the Gt(ROSA)26Sor locus with a loxP-flanked transcriptional stop sequence, in which successful Cre-mediated excision of the stop sequence is indicated by YFP expression in Cre-expressing cells. Administration of tamoxifen during early postnatal days (P4~7) induces Cre-dependent excision of stop sequences and allows YFP expression in proliferating neuronal progenitor cells in the external granule layer and Bergmann glia in the Purkinje cell layer. A substantial number of YFP-positive progenitor cells in the external granule layer migrated to the internal granule cell layer and became granule cell neurons. By comparison, injection of tamoxifen during late postnatal days (P19~22) induces YFP expression only in Bergmann glia, and most granule cell neurons were devoid of YFP expression. The results indicate that the Gli1 promoter is temporarily active in progenitor cells in the external granule layer during the early postnatal period but constitutively active in Bergmann glia. We propose that the Gli1-mediated CreER system can be applied for the conditional deletion of genes of interest from cerebellar granule cell neurons and/or Bergmann glia.

Evidence for PKD2L1-positive neurons distant from the central canal in the ventromedial spinal cord and medulla of the adult mouse.

Neurons in contact with the cerebrospinal fluid (CSF) are found around the medullo-spinal central canal (CC) in adult mice. These neurons (CSF-cNs), located within or below the ependymal cell layer, known as the stem cell niche, present a characteristic morphology with a dendrite projecting to the CC and ending with a protrusion. They are GABAergic, present an intermediate neuronal maturity and selectively express PKD2L1, a member of the transient receptor potential channel superfamily with sensory properties. Using immunohistological and electrophysiological recording techniques in mice, we characterize the properties of a new population of PKD2L1 positive cells that is distant from the CC in a zone enriched with astrocytes and ependymal fibers of the ventro-medial spinal cord and medulla. They appear around embryonic day 16 and their number increases up to early postnatal days. With development and the reorganization of the CC region, they progressively become more distant from the CC, suggesting some migratory capabilities. These neurons share functional and phenotypical properties with CSF-cNs but appear subdivided in two groups. One group, present along the midline, has a bipolar morphology and extends a long dendrite along ependymal fibers and towards the CC. The second group, localized in more ventro-lateral regions, has a multipolar morphology and no apparent projection to the CC. Altogether, we describe a novel population of PKD2L1+ neurons distant from the CC but with properties similar to CSF-cNs that might serve to sense modification in the composition of either CSF or interstitial liquid, a function that will need to be confirmed.

Use of Intranasal Insulin as Neuroprotection From Hyperglycemia in Rat Model of Extremely Preterm Infants

Background: Hyperglycemia is common in extremely preterm infants (EPI) and is a risk factor for increased mortality and morbidity, including abnormal neurodevelopment. Hippocampus-mediated cognitive deficits are common in this population. In a rat model of insulinopenic hyperglycemia, abnormal neurochemistry in the hippocampus was found, with lactate, glutamate (Glu):glutamine (Gln) ratio lower and Phosphorylated Creatinine (PCr):Creatinine (Cr) higher. Intranasal insulin has been shown to improve cognitive function in animal models of Alzheimer’s disease and type 2 diabetes mellitus, as well as in adult human studies of Alzheimer’s disease. No study has previous investigated the use of intranasal insulin on preventing the long-term effects of hyperglycemia in the EPI population. Objective: To determine whether administration of intranasal insulin during early postnatal days would negate the effects of hyperglycemia on the developing hippocampus in neonatal rat model of streptozotocin (STZ)-induced hyperglycemia. Design/Methods: STZ (80mg/kg IP) was injected on postnatal day (P) 2, and littermates in the control group were injected with an equivalent volume of citrate buffer. STZ pups were randomized to intranasal insulin, 3U twice daily from P3-P6 (STZ + INS) or left untreated (STZ). Neurochemical profile (consisting of 20 metabolites, PCr:Cr and Glu:Gln ratios) of the hippocampus was evaluated using ultra-high-field (9.4 T) magnetic resonance spectroscopy (MRS) on P7 (acute effects) and P56 (long-term effects) compared with the control group (CON)(N=6/group). Results: Mean glucose values from P3-P6 were higher in STZ groups (STZ = 279.0 +/- 132.2 mg/dL, STZ+INS = 274.4 +/- 89.5 mg/dL, CONT = 128.4 +/- 15.1 mg/dL). The neurochemical profile was different at both P7 and P56. On P7, compared with the control, the taurine (Tau) was higher in the STZ groups (p = 0.007. At P56, PCr:Cr was higher in the STZ group compared to CONT and STZ+INS groups (p = 0.04). No difference noted between the STZ+INS and CONT groups. No other metabolites were altered. Conclusion: Neonatal hyperglycemia alters the acute and long-term neurochemical profile in the hippocampus of developing rats. The increase in PCr:Cr ratio in the STZ group indicates lower demand for ATP and PCr, secondary to decreased neuronal activity, which has been demonstrated in previous studies. PCr:Cr ratio of the STZ+INS group was no different than control, indicating that intranasal insulin reverses the negative effect on neuronal activity caused by neonatal hyperglycemia.

Postnatal development of the mitochondrial reticulum in the cardiac muscles of mice

Adult cardiac muscles are characterized by well-developed mitochondrial networks, which supports high energy demand in the heart. However, it is obscure how these structures are formed during postnatal development. Using focused ion beam scanning electron microscopy (FIB-SEM), we collected high-resolution image stacks of cardiac muscles of mice at postnatal (P) day 1, 7, 14, and 42, respectively (N=2-3 per group). Then, we conducted a semi-automated machine running to extract 3D mitochondrial formations and analyzed its morphological characteristics across postnatal days. After forming more stretched structures by P7, it was shown that cardiac muscles further develop spherical shaped-mitochondria and that they are overall arranged in the fiber-parallel direction. Although total mitochondrial volumes tend to increase across P1-P42, individual mitochondrial volumes were relatively smaller during early postnatal days (P1-P14) than in the matured muscles. Notably, we observed that individual mitochondrial surface area to volume ratios as well as aspect ratios are significantly downregulated during the entire developmental period by ~34% and ~31%, respectively. Furthermore, it was also shown that individual mitochondrial lengths are ~31% decreased across the postnatal days. In conclusion, these preliminary results provide dynamic transitions of individual mitochondrial structures during postnatal cardiac muscle development. Nevertheless, further analyses will be needed to study intermitochondrial interactions, as well as mitochondrial interactions with other subcellular components (e.g., lipid droplets), by which we can better understand functional aspects of mitochondria in developing cardiac muscles.

RETRACTED: Maternal diabetes-induced alterations in the expression of brain-derived neurotrophic factor in the developing rat hippocampus

Maternal diabetes during pregnancy affects the development of hippocampus in the offspring. Brain-derived neurotrophic factor (BDNF) has received increasing attention for its role in regulating the survival and differentiation of neuronal cells in developing and adult brain. In the current study, we evaluated the effects of maternal diabetes and insulin treatment on expression and distribution pattern of BDNF in the hippocampus of neonatal rats at the first two postnatal weeks. We found no differences in hippocampal expression of BDNF between diabetics with normal control or insulin treated neonatal rats at postnatal day (P0) (P > 0.05 each). Nevertheless, there was a marked BDNF downregulation in both sides’ hippocampi of male/female diabetic group in two-week-old offspring (P ≤ 0.05 each). Furthermore, the numerical density of BDNF+ cells was significantly reduced in the right/left dentate gyrus (DG) of male and female newborns born to diabetic animals at all studied postnatal days (P ≤ 0.05 each). In addition, a lower number of reactive cells have shown in the all hippocampal subareas in the diabetic pups at P14 (P ≤ 0.05 each). Our results have demonstrated that the insulin-treatment improves some of the negative impacts of diabetes on the expression of hippocampal BDNF in the newborns. We conclude that diabetes in pregnancy bilaterally disrupts the expression of BDNF in the hippocampus of the both male and female newborns at early postnatal days. In addition, good glycemic control by insulin in the most cases is sufficient to prevent the alterations in expression of BDNF protein in developing hippocampus.

A Study of Maternal Breast Feeding Issues during Early Postnatal Days

Background: The success in breast-feeding is dependent on early initiation and effective management of breast feeding problems during early postnatal days. Objectives: To identify breast feeding problems and their etiologies during early postnatal days until discharge from hospital. Methodology: Descriptive study done in a medical college hospital. One hundred and twenty mothers in early postnatal days were enrolled in the study. Sick mothers, sick neonates admitted in NICU for >24 hours and where breast-feeding was contraindicated were excluded. Data was collected by direct interview with the mother by the investigators and were entered in the proforma. The questionnaire contained general information of the mothers, self-reported and observed problems about breast feeding. The first interview was carried out within 12 hours of delivery after taking informed consent. Follow up interviews were done on 24 hourly basis until discharge. Data was analyzed statistically. Results: Mothers were aged between 22 to 40 years with more than half in 26-30 years range. Majority were homemakers and educated up to high school. 31(25.8%) were primi mothers. 64(53%) had vaginal and 56(47%) had caesarean deliveries. 61.6% of the mothers knew about colostrum and its benefits. Most (98.3%) of the mothers felt that there is a need for education about breast-feeding. Majority had initiated breast feeds within an hour or at least within 4 hours (LSCS mothers). Insufficiency of milk and problems with latching, positioning and sucking were some of the problems noted. Though most of the problems were resolved before discharge, few persisted until discharge. Perceived milk insufficiency, latching problems and breast problems were higher in primi and found to be statistically significant. Objective problems like poor positioning, sucking etc were higher among primi and caesarean mothers. Even problems that remained at discharge were also more among them. Conclusions: Most common problems were positioning, emphasizing the need for teaching/training. Primi and delivery by LSCS were found to have higher feeding problems emphasizing the need to focus on these high risk groups. Doi: 10.28991/SciMedJ-2020-0204-4 Full Text: PDF

Long-Term, Serum-Free Cultivation of Organotypic Mouse Retina Explants with Intact Retinal Pigment Epithelium.

In ophthalmic research, there is a strong need for in vitro models of the neuroretina. Here, we present a detailed protocol for organotypic culturing of the mouse neuroretinawith intact retinal pigment epithelium (RPE). Depending on the research question, retinas can be isolated from wild-type animals or from disease models, to study, for instance, diabetic retinopathy or hereditary retinal degeneration. Eyes from early postnatal day 2-9 animals are enucleated under aseptic conditions. They are partially digested in proteinase K to allow for a detachment of the choroid from the RPE. Under the stereoscope, a small incision is made in the cornea creating two edges from where the choroid and sclera can be gently peeled off from the RPE and neuroretina. The lens is then removed, and the eyecup is cut in four points to give it a four-wedged shape resembling a clover leaf. The tissue is finally transferred in a hanging drop into a cell culture insert holding a polycarbonate culturing membrane. The cultures are then maintained in R16 medium, without serum or antibiotics, under entirely defined conditions, with a medium change every second day. The procedure described enables the isolation of the retina and the preservation of its normal physiological and histotypic context for culturing periods of at least 2 weeks. These features make organotypic retinal explant cultures an excellent model with high predictive value, for studies into retinal development, disease mechanisms, and electrophysiology, while also enabling pharmacological screening.

Agmatine improves the behavioral and cognitive impairments associated with chronic gestational ethanol exposure in rats

Chronic maternal ethanol exposure leads to poor intelligence, impaired cognition and array of neurological symptoms in offsprings and commonly referred as fetal alcohol spectrum disorder (FASD). Despite high prevalence and severity, the neurochemical basis of FASD remains largely unexplored. The present study evaluated the pharmacological effects of agmatine in cognitive deficits associated with FAS in rat’s offsprings prenatally exposed to alcohol. Pregnant rats received ethanol in liquid modified diet during the entire gestational period of 21 days. Offsprings were treated with agmatine (20–80 mg/Kg, i.p.) during early postnatal days (PND: 21–35) and subsequently evaluated for anxiety in elevated plus maze (EPM), depression in forced swim test (FST) and learning and memory in Morris’s water maze (MWM) during post adolescent phase. Hippocampal agmatine, BDNF, TNF-α and IL-6 levels were also analyzed in prenatally ethanol exposed pups. Offsprings prenatally exposed to ethanol demonstrated delayed righting reflex, reduced exploratory behavior along with anxiety, depression-like behavior and impaired memory. These behavioral abnormalities were correlated with a significant reduction in hippocampal agmatine and BDNF levels and elevation in TNF-α and IL-6 immunocontent. Chronic agmatine (40 and 80 mg/Kg, i.p.) administration for 15 days (PND: 21–35), improved entries and time spent in open arm of EPM, decreased immobility time in FST. It also reduced latency to reach the platform location; increased the number of entries, time spent in platform quadrant and also number of crossing over platform quadrant when subjected to MWM test in prenatally ethanol exposed offsprings. This study provides functional evidences for the therapeutic potential of agmatine in cognitive impairment and other neurological complications associated with FASD.

Evaluation of the Neurogenic Potential in the Rat Inferior Colliculus from Early Postnatal Days Until Adulthood

Neural stem cells (NSCs) have been recently identified in the inferior colliculus (IC). These cells are of particular interest, as no casual therapeutic options for impaired neural structures exist. This research project aims to evaluate the neurogenic potential in the rat IC from early postnatal days until adulthood. The IC of rats from postnatal day 6 up to 48 was examined by neurosphere assays and histological sections. In free-floating IC cell cultures, neurospheres formed from animals from early postnatal to adulthood. The amount of generated neurospheres decreased in older ages and increased with the number of cell line passages. Cells in the neurospheres and the histological sections stained positively with NSC markers (Doublecortin, Sox-2, Musashi-1, Nestin, and Atoh1). Dissociated single cells from the neurospheres differentiated and were stained positively for the neural lineage markers β-III-tubulin, glial fibrillary acidic protein, and myelin basic protein. In addition, NSC markers (Doublecortin, Sox-2, CDK5R1, and Ascl-1) were investigated by qRT-PCR. In conclusion, a neurogenic potential in the rat IC was detected and evaluated from early postnatal days until adulthood. The identification of NSCs in the rat IC and their age-specific characteristics contribute to a better understanding of the development and the plasticity of the auditory pathway and might be activated for therapeutic use.

Asymmetry of turning behavior in rats is modulated by early life stress

Atypical leftward behavioral asymmetries have been associated with early life stress and psychopathologies in humans and animals. Maternal separation (MS) is a frequently used model to investigate early life stress and psychopathologies but has not yet been studied in terms of asymmetries. This study aims to investigate whether prolonged MS induces atypical leftward asymmetries in the turning behavior of rats. MS was performed from postnatal days 2–20 followed by a second stressor from postnatal days 21−40. Asymmetry of turning behavior was then examined in the elevated plus-maze test upon weaning (juveniles and dams) or adolescence. The number of left and right turns was calculated per animal using the deep learning software package DeepLabCut enabling markerless pose estimation. Then, a lateralization quotient (LQ) was determined for each animal allowing to investigate the strength as well as the preferred side of asymmetry. LQ analysis revealed a significant leftward asymmetry in the prolonged stress group. Moreover, analyzing the number of turns revealed significantly more left than right turns in total in this group. Control animals showed no asymmetries in turning behavior. These results indicate that prolonged stress during the early postnatal days led to atypical leftward turning behavior. The stress-induced atypical asymmetry might be a mediator of early life stress and the development of psychiatric disorders.

Transient sublethal hypoxia in neonatal rats causes reduced dendritic spines, aberrant synaptic plasticity, and impairments in memory.

Hypoxic/ischemic insult, a leading cause of functional brain defects, has been extensively studied in both clinical and experimental animal research, including its etiology, neuropathogenesis, and pharmacological interventions. Transient sublethal hypoxia (TSH) is a common clinical occurrence in the perinatal period. However, its effect on early developing brains remains poorly understood. The present study was designed to investigate the effect of TSH on the dendrite and dendritic spine formation, neuronal and synaptic activity, and cognitive behavior of early postnatal Day 1 rat pups. While TSH showed no obvious effect on gross brain morphology, neuron cell density, or glial activation in the hippocampus, we found transient hypoxia did cause significant changes in neuronal structure and function. In brains exposed to TSH, hippocampal neurons developed shorter and thinner dendrites, with decreased dendritic spine density, and reduced strength in excitatory synaptic transmission. Moreover, TSH-treated rats showed impaired cognitive performance in spatial learning and memory. Our findings demonstrate that TSH in newborn rats can cause significant impairments in synaptic formation and function, and long-lasting brain functional deficits. Therefore, this study provides a useful animal model for the study of TSH on early developing brains and to explore potential pharmaceutical interventions for patients subjected to TSH insult.

Oxytocin ameliorates maternal separation-induced ultrasonic vocalisation calls in mouse pups prenatally exposed to valproic acid.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder estimated by the World Health Organization to occur in one of 160 children worldwide. No pharmaceutical treatments are available to improve the deficits in social communication that are common symptoms of ASD. Recent clinical trials have focused on the nasal application of oxytocin, a neuronal peptide known to regulate a variety of social behaviours. However, the effect of oxytocin on this deficit is inconclusive. By contrast, evidence from ASD animal model studies indicates that when animals are treated with oxytocin during early development, improvements in social deficits are observed in adulthood. Thus, it is necessary to examine the effect of therapeutic target medication prescribed in early development. Mice prenatally exposed to valproic acid (VPA) are widely used as an animal model of ASD. However, many behavioural studies have been conducted during adulthood rather than early development. To establish a screening system to identify therapeutic drugs that are effective when delivered during the early postnatal period, it is important to examine the early developmental changes in their communicative behaviours. In the present study, we examined the ultrasonic vocalisation (USV) of VPA-exposed mice pups during their early postnatal developmental days. USV rates were comparable to those of the controls until the first week of their life but declined more on postnatal day 11. We checked the expression of oxytocin system in the hypothalamus and found the down-regulation of oxytocin and CD38, and up-regulation of oxytocin receptor in the VPA pups. Acute administration of oxytocin on postnatal day 11 increased the call rate of VPA pups. Taken together, we have demonstrated there was a deficiency in the oxytocinergic signalling in the VPA pups and also shown the existence of time periods that are effective with respect to screening the therapeutic drugs.

Expression of Behavioral Phenotypes in Genetic and Environmental Mouse Models of Schizophrenia.

Schizophrenia is a neuropsychiatric disorder characterized by multifactorial etiology involving complex interactions among genetic and environmental factors. “Multiple-hit” models of the disorder can explain its variable incidence and prevalence in related individuals. Hence, there is a dire need to understand these interactions in the emergence of schizophrenia. To test these factors in the emergence of schizophrenia-like behaviors, we employed a genetic mouse model of the disorder (harboring the DISC1 mutation) along with various environmental insults, such as early life stress (maternal separation of pups) and/or pharmacological interventions (ketamine injections). When assessed on a battery of behavioral tests, we found that environmental interventions affect the severity of behavioral phenotypes in terms of increased negative behavior, as shown by reduced mobility in the forced swim and tail suspension tests, and changes to positive and cognitive symptoms, such as increased locomotion and disrupted PPI along with reduced working memory, respectively. Among the various interventions, the genetic mutation had the most profound effect on behavioral aberrations, followed by an environmental intervention by ketamine injections and ketamine-injected animals that were maternally separated during early postnatal days. We conclude that although environmental factors increased the prevalence of aberrant behavioral phenotypes, genetic background is still the predominant influence on phenotypic alterations in these mouse models of schizophrenia.

AMPA receptor deletion in developing MGE-derived hippocampal interneurons causes a redistribution of excitatory synapses and attenuates postnatal network oscillatory activity

Inhibitory interneurons derived from the medial ganglionic eminence represent the largest cohort of GABAergic neurons in the hippocampus. In the CA1 hippocampus excitatory synapses onto these cells comprise GluA2-lacking, calcium-permeable AMPARs. Although synaptic transmission is not established until early in their postnatal life, AMPARs are expressed early in development, however their role is enigmatic. Using the Nkx2.1-cre mouse line we genetically deleted GluA1, GluA2, GluA3 selectively from MGE derived interneurons early in development. We observed that the number of MGE-derived interneurons was preserved in mature hippocampus despite early elimination of AMPARs, which resulted in >90% decrease in spontaneous excitatory synaptic activity. Of particular interest, excitatory synaptic sites were shifted from dendritic to somatic locations while maintaining a normal NMDAR content. The developmental switch of NMDARs from GluN2B-containing early in development to GluN2A-containing on maturation was similarly unperturbed despite the loss of AMPARs. Early network giant depolarizing potential oscillatory activity was compromised in early postnatal days as was both feedforward and feedback inhibition onto pyramidal neurons underscoring the importance of glutamatergic drive onto MGE-derived interneurons for hippocampal circuit function.

DEVELOPMENT OF GIFTEDNESS DURING EARLY CHILDHOOD

Since the early postnatal days, gifted children seem to benefit more from the experience than their non gifted peers by developing increasingly efficient behaviors in more complex environments. Most of the models that try to explain this greater adaptability focus on the study of the higher cognitive functions and cortical regions that support them, However, during the early stages of development these areas are still functionally and structurally immature. The objective of this review is to synthesize and describe the subcortical and cortical neurobiological mechanisms that underlie the interaction with the environment, motivation for the practice and automation of higher cognitive processes in gifted children from the early stages of postnatal development.

Presence of Mother Reduces Early-Life Social Stress: Linking the Alteration in Hypothalamic-Pituitary-Adrenal Axis and Serotonergic System

In this study, we examined whether the presence of mother suppresses early-life stressful social experience (SSE)-induced anxiety-like behavior and impairment of short-term memory later in life. On postnatal day (PND)-5, mothers with pups were grouped as follows: (i) control; (ii) maternal separation (MS); (iii) pups with mother experience the presence of a stranger (M+P-ST); and (iv) maternal separated pups experience the presence of a stranger (MSP-ST). Individuals were subjected to light-dark box and spontaneous alternation from PND-29 to 32. We observed that the MSP-ST group exhibits anxiety-like behavior and impairment in short-term memory. Further, SSE significantly elevated the adrenocorticotropic hormone, corticosterone and expression of glucocorticoid receptor (GR) in MSP-ST pups. Similarly, serotonin (5-hydroxytryptamine; 5-HT), dopamine, noradrenaline and expression of serotonin transporter levels were significantly elevated in MSP-ST pups. These observations suggest that during early postnatal days, the pups may recognize strangers by the sense of smell, and the presence of mother reduces the SSE-induced stress.

Thyroxine modulation of immune toxicity induced by mixture pesticides mancozeb and fipronil in mice

AimThe cross regulation between neuroendocrine system, particularly Hypothalamus-Pituitary-Thyroid (HPT) axis and immune system during embryonic/early neonatal developmental stages shapes the functional attribute of immune response throughout the life. Thus, disruption of immune system was anticipated on exposure to thyroid disrupting pesticides (TDPs) mancozeb (MCZ) and fipronil (FPN) during critical windows of early postnatal days (PND) development. Main methodsMice were exposed to MCZ and FPN as individual (0.5% LD 50 each) and as mixtures (0.25% and 0.5% LD 50 each) from PND 31 (initiation phase of immune response) till PND 60 (Maturation phase). Thyroxine (T4) supplementation was given from PND 51 to PND 60. Assessment was done at PND 61 as well as at PND 91 (adults). Key findingsPlasma level of thyroid hormones (T3 and T4) was reduced but pituitary hormone (TSH) increased till adulthood on exposure to mixture pesticides but not on individual exposure. Mixture pesticides also increased body weight gain and reduced survival rate in adults. Exposure of individual pesticides exert immunotoxicity but more pronounced immune suppression was observed in mixture pesticides exposed group as reflected in reduced relative weight and cellularity in spleen and thymus, reduced in vitro mitogenic (Con A/LPS) response of splenocytes and thymocytes (reduced proliferative index and increased apoptotic/necrotic death). T4 supplementation ameliorated thyroid disruptive and immunotoxic effect of pesticides. SignificanceThe additive/synergistic toxicity as well as hypothyroidism induced by mixture pesticides has produced pronounced immune suppression that reflected till adulthood. Supplementation of T4 prevented thyroid axis disruption mediated immunosuppression.

Neonatal non-immune hydrops due to large placental chorioangioma -a treatable cause of hydrops

The term non-immunologic hydrops fetalis (NIHF) defines an edematous fetus with fluid collections in some usually two or all serous cavities that does not have erythroblastosis fetalis from isoimmunization. Ballantyne described the first case of non-immune hydrops. In 1943 Dr Edith Potter published the first description of NIHF. Hydrops Fetalis is considered as a prenatal form of cardiac failure. Hydrops may present as a stiffness of one limb due to edema (present case) to severe generalized anasarca with bilateral pleural effusion. Usually non-immune hydrops associated with severe morbidity and mortality. NIHF not only caused by fatal fetal causes like Chromosomal, alpha thalassemia, infections and cardiac causes but also caused by placental causes like twin to twin transfusion syndrome and placental tumours like placental chorioangioma, among these last entity usually have good prognosis if we managed properly in utero or at the time of delivery and early postnatal days. Some cases of non-immune hydrops amenable to treatment and will have better prognosis like chylothorax, CCAM, Supra Ventricular Tachycardia (SVT), bladder obstruction and hydrothorax.