Mother Mice Research Articles

Maternal Nicotine Exposure Alters Hippocampal Microglia Polarization and Promotes Anti-inflammatory Signaling in Juvenile Offspring in Mice.

Accumulating evidence reveal that maternal smoking or perinatal nicotine replacement therapy impairs hippocampal neurogenesis, neural development, and cognitive behaviors in the offspring. Microglia is a source of non-neural regulation of neuronal development and postnatal neurogenesis. In this study, we explored the impact of nicotine on the microglia during the development of hippocampus. Developmental nicotine exposure in a mouse model was conducted by supplementing nicotine in the drinking water to mother mice during gestation and lactation period. We found that juvenile offspring with maternal nicotine exposure presented physical and neurobehavioral development delay and an increase in anxiety-like behavior in the open field test on postnatal day (PND) 20. To further detect possible developmental neurotoxic effects of nicotine in offspring and underlying mechanism, whole genome microarray analysis of the expression profile of the hippocampus was performed on postnatal day 20. Significant alterations in the expression of genes related to inflammatory, neurotransmitter, and synapsis were observed in the hippocampus after maternal nicotine exposure, as compared to the vehicle control. Concurrently, an increase in microglial markers and the presence of M2 polarity state in the hippocampus of the nicotine offspring were observed by histological analysis and confocal z-stacking scanning. The M2 microglial polarization state was further confirmed with in vitro primary microglia culture by cytokine array, and double-positive expression of BDNF/Iba1 in microglia by immunohistochemical staining in the juvenile offspring hippocampus was visualized. We also found that nicotine offspring showed an increase of neurite length in the molecular layer and CA1 by Tuj1 staining, as well as an increase in the expression of synapse associated protein, PSD95, but the expression of NeuroD1 in CA1 and CA3 reduced. In summary, maternal nicotine exposure dysregulates immune-related genes expression by skewing the polarity of M2 microglia in the hippocampus, which may cause abnormal cognitive and behavioral performance in the offspring.

Maternal high sugar and fat diet benefits offspring brain function via targeting on the gut-brain axis.

A recent study showed that a gestational high fat diet protects 3xTg-AD offspring from memory impairments, synaptic dysfunction, and brain pathology. However, it is unknown whether this diet exerts the same effects on normal mice or on other functions, and if so, how. In the present study, mother mice were pre-fed a high sugar and high fat (HSHF) diet for 1 month and then fertilized; the HSHF diet was continued until birth and then mother mice were returned to a standard diet. The gut microbiota, and intestinal and brain functions of the offspring were dynamically monitored at 7, 14, 28, and 56 days old until 16 months of age. Results showed that the HSHF diet significantly affected the gut microbiota structure of the offspring, especially during the early life stage. In addition, in the HSHF diet offspring, there were influenced on various types of neurons, including cholinergic and GABAergic neurons, on autophagy levels in the brain, and on inflammation levels in the intestinal tract. When the offspring grew older (16 months), we found that some genes of benefit against nervous system disease were activated, such as Lhx8, GPR88, RGS9, CD4, DRD2, RXRG, and Syt6, and the expression of cholinergic and GABAergic neurons biomarker protein increased. Although the inflammation levels in the nervous and peripheral systems showed no obvious differences, the AFP level of individuals on the HSHF diet was much higher than those on the standard diet, suggesting that more accurate and/or personalized nutrition is needed. Taken together, the results show that a maternal HSHF diet benefits the offspring by reducing the risk of nervous diseases, which might depend on LHX8 activation to modulate cholinergic and GABAergic neurons via the gut–brain axis, but still need much more deep studies.

Receptor for advanced glycation end-products (RAGE) plays a critical role in retrieval behavior of mother mice at early postpartum

Receptor for advanced glycation end-products (RAGE) is a pattern recognition molecule belonging to the immunoglobulin superfamily, and it plays a role in the remodeling of endothelial cells under pathological conditions. Recently, it was shown that RAGE is a binding protein for oxytocin (OT) and a transporter of OT to the brain on neurovascular endothelial cells via blood circulation. Deletion of the mouse RAGE gene, Ager (RAGE KO), induces hyperactivity in male mice. Impairment of pup care by mother RAGE KO mice after stress exposure results in the death of neonates 1-2 days after pup birth. Therefore, to understand the role of RAGE during the postpartum period, this study aims to examine parental behavior in female RAGE KO mice and ultrasonic vocalizations in pups. RAGE KO mothers without stress before delivery raised their pups and displayed hyperactivity at postpartum day (PPD) 3. KO dams showed impaired retrieval or interaction behavior after additional stress, such as body restraint stress or exposure to a novel environment, but such impaired behavior disappeared at PPD 7. Postnatal day 3 pups emitted ultrasonic vocalizations at >60kHz as a part of the mother-pup relationship, but the number and category of calls by RAGE KO pups were significantly lower than wild-type pups. The results indicate that RAGE is important in the manifestation of normal parental behavior in dams and for receiving maternal care by mouse pups; moreover, brain OT recruited by RAGE plays a role in damping of signals of additional external stress and endogenous stress during the early postpartum period. Thus, RAGE-dependent OT may be critical for initiating and maintaining the normal mother-child relationship.

Chloroquine, an Anti-Malaria Drug as Effective Prevention for Hantavirus Infections

We investigated whether chloroquine can prevent hantavirus infection and disease in vitro and in vivo, using the Hantaan virus newborn C57BL/6 mice model and the Syrian hamster model for Andes virus. In vitro antiviral experiments were performed using Vero E6 cells, and Old World and New World hantavirus species. Hantavirus RNA was detected using quantitative RT-PCR. For all hantavirus species tested, results indicate that the IC50 of chloroquine (mean 10.2 ± 1.43 μM) is significantly lower than the CC50 (mean 260 ± 2.52 μM) yielding an overall selectivity index of 25.5. We also investigated the potential of chloroquine to prevent death in newborn mice after Hantaan virus infection and its antiviral effect in the hantavirus Syrian hamster model. For this purpose, C57Bl/6 mother mice were treated subcutaneously with daily doses of chloroquine. Subsequently, 1-day-old suckling mice were inoculated intracerebrally with 5 x 102 Hantaan virus particles. In litters of untreated mothers, none of the pups survived challenge. The highest survival rate (72.7% of pups) was found when mother mice were administered a concentration of 10 mg/kg chloroquine. Survival rates declined in a dose-dependent manner, with 47.6% survival when treated with 5 mg/kg chloroquine, and 4.2% when treated with 1 mg/kg chloroquine. Assessing the antiviral therapeutic and prophylactic effect of chloroquine in the Syrian hamster model was done using two different administration routes (intraperitoneally and subcutaneously using an osmotic pump system). Evaluating the prophylactic effect, a delay in onset of disease was noted and for the osmotic pump, 60% survival was observed. Our results show that chloroquine can be highly effective against Hantaan virus infection in newborn mice and against Andes virus in Syrian hamsters.

A Long-Term Enriched Environment Ameliorates the Accelerated Age-Related Memory Impairment Induced by Gestational Administration of Lipopolysaccharide: Role of Plastic Mitochondrial Quality Control.

Studies have shown that gestational inflammation accelerates age-related memory impairment in mother mice. An enriched environment (EE) can improve age-related memory impairment, whereas mitochondrial dysfunction has been implicated in the pathogenesis of brain aging. However, it is unclear whether an EE can counteract the accelerated age-related memory impairment induced by gestational inflammation and whether this process is associated with the disruption of mitochondrial quality control (MQC) processes. In this study, CD-1 mice received daily intraperitoneal injections of lipopolysaccharide (LPS, 50 μg/kg) or normal saline (CON group) during gestational days 15–17 and were separated from their offspring at the end of normal lactation. The mothers that received LPS were divided into LPS group and LPS plus EE (LPS-E) treatment groups based on whether the mice were exposed to an EE until the end of the experiment. At 6 and 18 months of age, the Morris water maze test was used to evaluate spatial learning and memory abilities. Quantitative reverse transcription polymerase chain reaction and Western blot were used to measure the messenber RNA (mRNA) and protein levels of MQC-related genes in the hippocampus, respectively. The results showed that all the aged (18 months old) mice underwent a striking decline in spatial learning and memory performances and decreased mRNA/protein levels related to mitochondrial dynamics (Mfn1/Mfn2, OPA1, and Drp1), biogenesis (PGC-1α), and mitophagy (PINK1/parkin) in the hippocampi compared with the young (6 months old) mice. LPS treatment exacerbated the decline in age-related spatial learning and memory and enhanced the reduction in the mRNA and protein levels of MQC-related genes but increased the levels of PGC-1α in young mice. Exposure to an EE could alleviate the accelerated decline in age-related spatial learning and memory abilities and the accelerated changes in MQC-related mRNA or protein levels resulting from LPS treatment, especially in aged mice. In conclusion, long-term exposure to an EE can counteract the accelerated age-related spatial cognition impairment modulated by MQC in CD-1 mother mice that experience inflammation during pregnancy.

Effects of Perinatal Tcdd Exposure on Colonic Microbiota and Metabolism in Offspring and Mother Mice

Effects of Perinatal Tcdd Exposure on Colonic Microbiota and Metabolism in Offspring and Mother Mice

Enhanced Discriminative Abilities of Auditory Cortex Neurons for Pup Calls Despite Reduced Evoked Responses in C57BL/6 Mother Mice

A fundamental task for the auditory system is to process communication sounds according to their behavioral significance. In many mammalian species, pup calls became more significant for mothers than other conspecific and heterospecific communication sounds. To study the cortical consequences of motherhood on the processing of communication sounds, we recorded neuronal responses in the primary auditory cortex of virgin and mother C57BL/6 mice which had similar ABR thresholds. In mothers, the evoked firing rate in response to pure tones was decreased and the frequency receptive fields were narrower. The responses to pup and adult calls were also reduced but the amount of mutual information (MI) per spike about the pup call’s identity was increased in mother mice. The response latency to pup and adult calls was significantly shorter in mothers. Despite similarly decreased responses to guinea pig whistles, the response latency, and the MI per spike did not differ between virgins and mothers for these heterospecific vocalizations. Noise correlations between cortical recordings were decreased in mothers, suggesting that the firing rate of distant neurons was more independent from each other. Together, these results indicate that in the most commonly used mouse strain for behavioral studies, the discrimination of pup calls by auditory cortex neurons is more efficient during motherhood.

Poly I:C‐induced maternal immune challenge reduces perineuronal net area and raises spontaneous network activity of hippocampal neurons in vitro

Activation of the maternal immune system (MIA) during gestation is linked to neuropsychiatric diseases like schizophrenia. While many studies address behavioural aspects, less is known about underlying cellular mechanisms. In the following study, BALB/c mice received intraperitoneal injections of polyinosinic-polycytidylic acid (Poly I:C) (20µg/ml) or saline (0.9%) at gestation day (GD) 9.5 before hippocampal neurons were isolated and cultured from embryonic mice for further analysis. Interestingly, strongest effects were observed when the perineuronal net (PNN) wearing subpopulation of neurons was analysed. Here, a significant reduction of aggrecan staining intensity, area and soma size could be detected. Alterations of PNNs are often linked to neuropsychiatric diseases, changes in synaptic plasticity and in electrophysiology. Utilizing multielectrode array analysis (MEA), we observed a remarkable increase of the spontaneous network activity in neuronal networks after 21days in vitro (DIV) when mother mice suffered a prenatal immune challenge. As PNNs are associated with GABAergic interneurons, our data indicate that this neuronal subtype might be stronger affected by a prenatal MIA. Degradation or damage of this subtype might cause the hyperexcitability observed in the whole network. In addition, embryonic neurons of the Poly I:C condition developed significantly shorter axons after five days in culture, while dendritic parameters and apoptosis rate remained unchanged. Structural analysis of synapse numbers revealed an increase of postsynaptic density 95 (PSD-95) puncta after 14 DIV and an increase of presynaptic vesicular glutamate transporter (vGlut) puncta after 21 DIV, while inhibitory synaptic proteins were not altered.

Low maternal licking/grooming stimulation increases pain sensitivity in male mouse offspring.

Deprivation of maternal care has been associated with higher pain sensitivity in offspring. In the present study, we hypothesized that the maternal licking/grooming behavior was an important factor for the development of the pain regulatory system. To test this hypothesis, we used male F2 offspring of early-weaned (EW) F1 mother mice that exhibit lower frequency of licking/grooming behavior. The formalin test revealed that F2 offspring of EW F1 dams showed significantly higher pain behavior than F2 offspring of normally-weaned (NW) F1 dams. We found that the mRNA levels of transient receptor potential vanilloid 1 (TRPV1), a nociceptor, were higher in the lumbosacral dorsal root ganglion (DRG) of F2 offspring of EW F1 dams than those of F2 offspring of NW F1 dams, suggesting that the higher pain sensitivity may be attributed to low licking/grooming, which may result in developmental changes in nociceptive neurons. In the DRG, mRNA levels of Mas-related G-protein coupled receptor B4 (MrgprB4), a marker of sensory neurons that detect gentle stroking, was also up-regulated in the F2 offspring of EW F1 dams. Considering that gentle touch alleviates pain, Mrgprb4 up-regulation may reflect a compensatory change. The present findings indicate important implications of maternal licking/grooming behavior in the development of the pain regulatory system.

Maternal microbiome regulation prevents early allergic airway diseases in mouse offspring.

Asthma is a serious global health problem, severely affecting the lives of sufferers and their families. An exceptionally hygienic home and reduced microbial exposure can aggravate the incidence of childhood asthma. Specific-pathogen-free BALB/c mice were pre-treated with bacterial lysate (BL; 1mg/kg) as a high microbial load maternal mouse model, and then, the offspring mice were established as an allergic airway disease (AAD) model. The expression levels of TLR2, TLR4, and HDAC9 in the mother's intestine and the offspring's lungs were detected. Relevant indicators of regulatory T cells (Tregs) were identified in the mother and offspring mice. The changes in the expression of Th1-, Th2-, Th9-, and Th17-related cytokines in the offspring mice were evaluated among different pre-treated groups. After augmenting the mothers' intestinal microbiota through oral BL gavage, the expression of TLR2 and TLR4 in the colon mucosa and colon lymphoid tissues was enhanced and that of HDAC9 in the colon mucosa was decreased, and the proportion of spleen Tregs was increased. The offspring showed similar changes in the AAD model compared with the offspring of the control-group mothers: TLR2 and TLR4 expression in the lungs and the proportion of spleen Tregs increased, HDAC9 expression in the lungs decreased, and AAD-induced airway pathologic characteristics were reversed; additionally, Th1/Th2 and Th9 imbalances were rectified. This study presents a new framework for the prevention of childhood asthma, elucidating the mechanism of regulating the mother's intestinal microbiome to protect the offspring's early asthma via animal experiments.

Mother mice tune in to pup calls.

The temporal association cortex, a higher cortical area, of mother mice becomes tuned to pups’ ultrasonic vocalizations.

Hippocampus is more vulnerable to neural damages induced by repeated sevoflurane exposure in the second trimester than other brain areas.

During the rapidly developing and sensitive period of the central nervous system (CNS), a harmful stimulus may have serious consequences. The effect of anesthetic exposure on the development of the offspring's CNS during pregnancy is still unclear and has been widely concerned. In the present study, we compared the susceptibility of the hippocampus with those of other brain regions in offsprings when the mother mice were exposed to repeated sevoflurane. We found that other than affecting motor sensation, emotion, or social behavior of offspring mice, repeated sevoflurane exposure induced significant memory deficiency. Compared with other brain regions, the hippocampus, which is the key component of the brain serving for learning and memory, was more vulnerable to repeated sevoflurane exposure. We also found that repeated sevoflurane exposure to mother mice could inhibit the axon development of hippocampal neurons. We also predicted that N6-methyladenosine modification of mRNA might play an essential role in the vulnerability of the hippocampus to sevoflurane, while the underlying cellular mechanism needs to be explored in the future. Our study may provide a new perspective for studying the mechanism of hippocampus-specific injury induced by sevoflurane exposure.

Establishing a high microbial load maternal-offspring asthma model in adult mice

BackgroundAlthough it is widely accepted that the “hygiene hypothesis” explains the increased incidence of asthma, the lack of suitable animal models hinders further in-depth studies of the underlying molecular immune mechanisms. Therefore, we aimed to develop a robust mouse asthma model to investigate the role of bacteria in preventing asthma. MethodsBALB/c female mice were fed a mixture of eight common bacterial lysates (BL; Broncho-Vaxom®) and a commercial probiotic (Bifidobacterium tetravaccine tablets) at different concentrations before and during pregnancy to simulate different microbial load levels. Faeces from the mother mice were subjected to bacterial 16S rRNA sequencing to quantify the maternal microbial load. TLR2/4 expression and the proportion of regulatory T cells (Tregs) in the intestinal tract of female mice were determined, and the safety of the microbial load was evaluated. An asthma model was established in the offspring mice after weaning, and the extent of pulmonary pathological changes and Treg proportion were evaluated. ResultsA BL concentration of 1 mg/kg enriched the intestinal flora, increased the proportion of Tregs, and increased the expression of TLR2/4 in the maternal mice. The proportion of peripheral blood Tregs was increased, whereas the risk of asthma decreased only in the offspring from mothers with a high microbial load relative to control mice. ConclusionThis study established a safe and stable high microbial load maternal-offspring mouse asthma model, laying the foundation for a study on the molecular mechanism underlying the protective effects of a high microbial load against asthma.

Dibutyl phthalate exposure during gestation and lactation in C57BL/6 mice: Maternal behavior and neurodevelopment in pups

ObjectivesNeurotoxic effects of phthalate during pregnancy on immature brain of the offspring or mature brains of the mothers remain unclear. We examined the effect of dibutyl phthalate (DBP) exposure during gestation and lactation on the maternal behavior of mother mice and neurodevelopment in pups. MethodsPregnant mice were treated orally with DBP (0, 50 and 100 mg/kg/day, N = 20 per group) from gestational day 13 to postnatal day (PND) 15. Maternal behavior was measured using pup retrieval and nest shape test at postpartum day 4. For the pups, the neurodevelopment was measured using negative geotaxis, cliff avoidance at PND 7, swimming test and olfactory orientation at PND 14. RNA and protein expressions in the brain cortex of 50 mg/kg/day and control group (0 mg/kg/day) were analyzed using microarray and Western blot analysis. Nissl-stained sections at the coronal level of interaural 2.56 mm, bregma −1,23 mm, were used for counting of dark cortical neurons in mother and pup mice. ResultsDBP treated mother mice (50 and 100 mg/kg/day) showed poor maternal behavior, poor nesting and retrieval behavior compared to the control group (0 mg/kg/day). In brain cortex, DBP-treated mothers showed decrease in protein expression of Nr4a3, Egr1, Arc, BDNF and phosphorylation of AKT and CREB, were also decreased in cortex of DBP-treated mothers. Pups exposed to DBP showed significantly decreased scores in negative geotaxis at PND 7 and swimming scores and olfactory orientation tests at PND 14. The cortex of the DBP exposed pups showed increase in expression of dopamine receptor D2 gene. Nissl staining showed that the dark neurons were increased in cortex of DBP treated mothers and DBP exposed pups. Suggesting that phthalate may delay pup development indirectly through inadequate mothering as well as direct phthalate exposure on the brain. ConclusionDBP exposure during gestation and lactation cause impairment in maternal behaviors and downregulation of neuronal plasticity and survival signals. Pups of mothers with exposed to DBP, showed delayed neurodevelopment and dark neurons increase in brain cortex, suggesting that phthalate may delay pup development indirectly through inadequate mothering as well as direct phthalate exposure on the brain.

Effects of arsenic exposure on D-serine metabolism in the hippocampus of offspring mice at different developmental stages.

The main purpose of this study was to verify the hypothesis that cognitive dysfunctions induced by arsenic exposure were related to the changes of D-serine metabolism in the hippocampus of offspring mice. Mother mice and their offsprings were exposed to 0, 15, 30 or 60mg/L sodium arsenite (NaAsO2) through drinking water from the first day of gestation until the end of lactation. D-serine levels in the hippocampus of mice of postnatal day (PND) 10, 20 and 40 were examined by high-performance liquid chromatography. Expressions of serine racemase (SR), D-amino acid oxidase (DAAO), alanine-serine-cysteine transporter-1 (asc-1) and subunits of N-methyl-D-aspartate receptors (NMDARs) in the hippocampus of mice were measured by Western blot and Real-time RT-PCR. Results showed that arsenic exposure significantly decreased D-serine levels of mice exposed to 60mg/L NaAsO2. Exposure to 60mg/L NaAsO2 could inhibit both mRNA and protein expression of SR, whereas increase in the protein expression of DAAO, only enhances the mRNA levels of DAAO of PND 20 mice. In addition, arsenic exposure could upregulate protein expression of asc-1. The mRNA and protein levels of NR1, NR2A and NR2B in the hippocampus of mice were down-regulated by arsenic. Findings from this study suggested that SR might play an important role in the reduction of D-serine levels caused by arsenic exposure, which might further influence the levels of NMDAR subunits especially on PND20, and then might disturb the function of NMDARs and cause the deficits of learning and memory ability of offspring mice.

Low maternal care enhances the skin barrier resistance of offspring in mice.

Deprivation of maternal care via lack of somatosensory input causes offspring to experience adverse consequences, especially in the central nervous system. However, little is known about the developmental effect of maternal care on peripheral tissues such as the skin, which includes cutaneous sensory neurons. In the present study, we examined the involvement of maternal care in the development of the skin. We investigated offspring reared by early-weaned mother mice who spontaneously showed lower frequency of licking/grooming on nursing. Offspring of early-weaned mothers showed higher resistance against skin barrier disruption than did offspring of normally-weaned mothers, and had normal skin barrier function in the intact trunk skin. In the dorsal root ganglion of early-weaned mother offspring, we also found up-regulation of mRNA levels of the Mas-related G-protein coupled receptor B4 (MrgprB4), which is a marker of sensory neurons that detect gentle stroking. We further found that levels of MrgprB4 mRNA were correlated with the enhancement of skin resistance. The present findings suggest that maternal somatosensory inputs have a developmental impact on the cutaneous sensory neurons of the skin in offspring. Interestingly, the present results suggest that lower maternal care has a benefit on the skin resistance. This provides important information for understanding the development of peripheral tissues in offspring reared under severe conditions such as lower maternal care in the wild.

S907 DEVELOPMENT OF HUMANIZED MOUSE MODEL FOR STUDYING MOTHER TO CHILD HTLV‐1 TRANSMISSION AND PREVENTION WITH HTLV‐1 ANTIBODY TREATMENT

Background:Human T‐cell leukemia virus type 1 (HTLV‐1) infects mature T cells and causes adult T‐cell leukemia (ATL) and a chronic inflammatory central nervous system disease called HAM/TSP. HTLV‐1 transmissions mainly occurred in children via the breast milk of HTLV‐1+ carrier mothers. Thus, bottle‐feeding or avoiding long term breastfeeding are recommended in the endemic areas of Japan and this resulted in a drastic decrease in new HTLV‐1 infections. Previous studies have shown that approximately 3% of children born from HTLV‐1+ carrier mothers were still infected even when they were exclusively bottle‐fed. This suggested the possible involvement of alternative HTLV‐1 transmission routes, such as placental or birth canal transmission.Aims:Here, we attempted to develop new humanized mouse model of HTLV‐1 mother to child (MTC) transmission for evaluating HTLV‐1 antibody to prevent HTLV‐1 MTC infection.Methods:NOD/SCID/gammac (null) (NOG) pregnant mice were intraperitoneally injected with human PBMCs before being transplanted with a mitomycin C‐treated HTLV‐1‐infected cell line (MT‐2). To evaluate the importance of HTLV‐1 infections via breastfeeding or before birth, we designed a study that switched HTLV‐1‐infected carrier mother (CM) mice with non‐infected healthy mother (HM) mice. HTLV‐1 infection was determined by the real‐time PCR quantification of HTLV‐1 DNA isolated from mouse liver, peripheral blood and breastmilk.Results:Although no HTLV‐1‐infected T cells were detected in the peripheral blood of newborn mice at day 14, HTLV‐1‐infected cells were exclusively observed in the liver tissues via FACS and PCR. Furthermore, highly enriched HTLV‐1+ cells were still detected in mouse breast milk 26 days after birth by PCR. These data suggest that there might be an enrichment system of HTLV‐1 infectious cells in mouse breast tissue. We next performed the mother‐pup pair switching study. After switching, CM mice were maintained with HM mice pups (potentially HTLV‐1−), and HM mice were maintained with CM mice pups (potentially HTLV‐1+). This switching at birth resulted in 28% of the potentially HTLV‐1− pups to become HTLV‐1+, since they were breastfed by an HTLV‐1+ mother. Similarly, 42% of the potentially HTLV‐1+ pups were HTLV‐1+ at 40 days after switching, as they were breastfed by an HTLV‐1− mother. These results suggested that both breastfeeding and canal or placental transmissions presented equal risks with respect to HTLV‐1 infections. We finally analyzed the HTLV‐1 infectious status both in mouse embryo and placenta at E17.5 and found HTLV‐1+ cells both in fetal liver (25%) and placenta (37%).Summary/Conclusion:Together, these data suggest that during pregnancy, HTLV‐1 cells invade the fetal tissues and might be a potential resource of HTLV‐1 infection. We are now trying to assess the effect of HTLV‐1 antibody for preventing MTC HTLV‐1 infection.

Comparative Investigation of the Levels of BDNF and NGF Genes Expressions in the Brains of Male and Female Newborn Methimazole-Induced hypothyroidism in NMRI mice

One of the endocrine glands that play a significant role in the development of the prenatal brain is Thyroid. Therefore, the aim of this study is to compare the levels of BDNF and NGF gene expressions in the brains of male and female babies born on the first day methimazole-induced hypothyroidism Mice with NMRI race. In this study, 30 mature mice of Albino NMRI race were selected. Mice (Albino NMRI) were identified using after mating. In the next stage, we divided mice into three groups (high-dose intervention, low-dose intervention and control groups). Pure water was given during pregnancy to the control group. In the low dose group until the end of pregnancy given 20 mg of methimazole that dissolved in 100 cc of water. Also, in the high-dose group during period pregnancy until the end, they were given 100 mg of methimazole that dissolved in 100 cc of water. After the end of pregnancy, blood samples were taken from the mother's mice to determine the amount of T3 and T4 present in the bloodstream. In the end stage, the brain of one-day mice was removed and to determine the expression of BDNF, NGF we used to RT-PCR. According to the result this study, amount of T4 and T3 in the control group and low dose (27 and 1.59 ng/dl, and 8 and 0.87 ng/dl), respectively indicating a significant reduction in the expression of NT4, NT3, NGF and BDNF gene (P<0.05). Based on result of this study, between the high dose and control group there was significant relationship reduction in the expression (P<0.05).

Alterations of NMDA and AMPA receptors and their signaling apparatus in the hippocampus of mouse offspring induced by developmental arsenite exposure.

Loss of cognitive function due to arsenic exposure is a serious health concern in many parts of the world, including China. The present study aims to determine the molecular mechanism of arsenic-induced neurotoxicity and its consequent effect on downstream signaling pathways of mouse N-methyl-D-aspartate receptors (NMDARs) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Drinking water containing 0, 25, 50 or 100 mg/L arsenite was provided each day to mother mice throughout gestation period until postnatal day (PND) 35 to expose the newborn mice to arsenite during early developmental period. The effect of arsenite in the expressions of different components of NMDAR (NR1, NR2A, NR2B) and AMPAR (GluR1, GluR2, GluR3), including calcium/calmodulin-dependent protein kinase II (CaMKII) and phosphorylated-CaMKII (p-CaMKII), at PND 7, 14, 21 and 35 was estimated and analyzed from the hippocampus of mice. A significant inhibition in the protein and mRNA expressions of NR1, NR2A, NR2B and GluR1 was observed in mice exposed to 50 mg/L arsenite since PND 7. Down regulation of GluR2 and GluR3 both at mRNA and protein levels was observed in mice exposed to 50 mg/L arsenite till PND 14. Moreover, both CaMKII as well as p-CaMKII expressions were significantly limited since PND 7 in 50 mg/L arsenite exposed mice group. Findings form this study suggested that the previously reported impairment in learning and memorizing abilities in later stage due to early life arsenite exposure is associated with the alterations of NMDARs, AMPARs, CaMKII and p-CaMKII expressions.

Prolactin-induced and neuronal activation in the brain of mother mice.

Nursing has important consequences on mothers. To separate the prolactin-mediated and the neuronally-mediated actions of nursing, neurons directly affected by prolactin were visualized using pSTAT5 immunohistochemistry in relation to Fos-expressing neurons in suckled mother mice. In response to pup exposure following 22-h pup deprivation, we found a markedly elevated number of pSTAT5-containing neurons in several brain regions, including the lateral septum, medial amygdaloid nucleus, subparafascicular area, caudal periaqueductal gray, dorsal raphe, lateral parabrachial nucleus, nucleus of the solitary tract, and the periventricular, medial preoptic, paraventricular, arcuate and ventromedial nuclei of the hypothalamus. Pup exposure also induced Fos expression in all of these brain regions except the arcuate and ventromedial hypothalamic nuclei. Bromocriptine treatment known to reduce prolactin levels eliminated pSTAT5 from most brain regions while it did not affect Fos activation following suckling. The degree of colocalization for pSTAT5 and Fos ranged from 8 to 80% in the different brain regions suggesting that most neurons responding to pup exposure in mother mice are driven either by prolactin or direct neuronal input from the pups, while the number of neurons affected by both types of inputs depends on the examined brain area. In addition, both pSTAT5 and Fos were also double-labeled with estrogen receptor alpha (ERα) in mother mice, which revealed a very high degree of colocalization between pSTAT5 and ERα with much less potential interaction between Fos- and ERα-containing neurons suggesting that estrogen-sensitive neurons are more likely to be affected by prolactin than by direct neuronal activation.