Hippocampus Of Offspring Rats Research Articles

Severe Uncontrolled Maternal Hyperglycemia Induces Microsomia and Neurodevelopment Delay Accompanied by Apoptosis, Cellular Survival, and Neuroinflammatory Deregulation in Rat Offspring Hippocampus.

Maternal diabetes constitutes an unfavorable intrauterine environment for offspring development. Although it is known that diabetes can cause brain alterations and increased risk for neurologic disorders, the relationship between neuroimmune activation, brain changes, and neurodevelopment deficits in the offspring remains unclear. In order to elucidate the short- and long-term biological basis of the developmental outcomes caused by the severe uncontrolled maternal hyperglycemia, we studied apoptosis, neurogenesis, and neuroinflammation pathways in the hippocampus of neonates and young rats born to diabetic dams. Diabetes was induced on gestational day 5 by an injection of streptozotocin. Evaluations of milestones, body growth, and inhibitory avoidance were performed to monitor the offspring development and behavior. Hippocampal modifications were studied through cellular survival by BrdU in the dentate gyrus, expression of apoptosis-regulatory proteins (procaspase 3, caspase 3, and Bcl-2), BDNF, and neuroinflammatory modulation by interleukins, MHC-I, MHC-II, Iba-1, and GFAP proteins. Severe maternal diabetes caused microsomia and neurodevelopmental delay in pups and decrease of Bcl-2, procaspase 3, and caspase 3 in the hippocampus. Moreover, in a later stage of development, it was found an increase of TNF-α and a decrease of procaspase 3, caspase 3, MHC-I, IL-1β, and BDNF in the hippocampus, as well as impairment in cellular survival in the dentate gyrus. This study showed significant short- and long-term commitments on the development, apoptosis, cell survival, and neuroinflammation in the offspring hippocampus induced by severe uncontrolled maternal hyperglycemia. The data reinforce the need for treatment of maternal hyperglycemic states during pregnancy and breast-feeding.

Gestational stress induced differential expression of HDAC2 in male rat offspring hippocampus during development

Accumulating evidence from preclinical and clinical studies indicates prenatal exposure to stress or excess glucocorticoids can affect offspring brain. HDAC2 is an important target of glucocorticoid. Here we detected HDAC2 expression in male offspring hippocampus from gestational restraint stressed rat during development and the relationship between HDAC2 expression and behaviors and neurogenesis in male offspring. Pregnant rats received restrained stress during the last week of pregnancy. Expressions of HDAC2 in offspring hippocampus were detected on postnatal 0 day (P0) and 60 days (P60). Neurogenesis was evaluated by Doublecortin (DCX) staining on P60. Anxiety-like behavior and cognition were detected in open field, elevated plus maze, novel object recognition test, and Barnes maze. We found that HDAC2 expression in the hippocampus of male prenatally stressed offspring (MPSO) was similar to the male control offspring on P0, but significantly lower on P60. Corresponding to the decreased expression of HDAC2 in MPSO hippocampus at P60, neurogenesis in the dentate gyrus of MPSO was significantly lower than the control male offspring. And MPSO also showed greater anxiety and poorer learning and memories abilities than control male offspring. These showed that HDAC2 could partly explain the effects of gestational stress on male offspring behaviors.

Corrigendum: Prenatal Deltamethrin Exposure-Induced Cognitive Impairment in Offspring Is Ameliorated by Memantine Through NMDAR/BDNF Signaling in Hippocampus.

[This corrects the article DOI: 10.3389/fnins.2018.00615.].

Prenatal Deltamethrin Exposure-Induced Cognitive Impairment in Offspring Is Ameliorated by Memantine Through NMDAR/BDNF Signaling in Hippocampus.

Background: Pyrethroids have been widely used in residential and agricultural areas. However, little is known about the effects of prenatal exposure to deltamethrin on cognition in early development of offspring. In this study, the effects of prenatal exposure to deltamethrin on learning and memory abilities, N-methyl-D-aspartate receptor (NMDAR) subunits, brain derived neurotrophic factor (BDNF), Tyrosine kinase B (TrkB) receptor, and phosphorylated cAMP response element binding protein (pCREB) in the hippocampus of offspring rats were investigated.Experimental Approaches: Groups each of six female SD rats, as F0-generation, were administered with deltamethrin (0, 0.54, 1.35, and 2.7, 9 mg/kg), or memantine (10 mg/kg), or co-administered with deltamethrin (9 mg/kg) and memantine (10 mg/kg) daily by gavage during pregnancy. The learning and memory ability was evaluated using Morris water maze (MWM) task on postnatal day 21. The expression of NMDAR (GluN1, GluN2A, and GluN2B), BDNF, pTrkB/TrkB, and pCREB/CREB in hippocampus were assessed with western blotting.Results: Prenatal exposure to a relatively low dose of deltamethrin (2.7, 1.35, and 0.54 mg/kg) had no impact on learning and memory abilities or the expression of NMDAR, BDNF, pTrkB, and pCREB in the hippocampus of the exposed offspring. The group treated with 9 mg/kg deltamethrin showed impaired cognitive abilities and decreased expression levels of GluN1, GluN2A, GluN2B, BDNF, pCREB/CREB, and pTrkB/TrkB in the hippocampus. However, the declined cognitive ability were ameliorated by memantine treatment with increased GluN1, GluN2A, GluN2B, BDNF, pCREB/CREB, and pTrkB/TrkB expression in the hippocampus.Conclusion and Implications: Prenatal exposure to a relatively high does of deltamethrin (9 mg/kg) alters cognition in offsprings and that this cognitive dysfunction can be ameliorated by memantine treatment. Moreover, NMDAR/BDNF signaling may be associated with the effects of prenatal exposure to deltamethrin on cognitive ability in offspring.

Beyond the maternal epigenetic legacy.

In 2004, Weaver et al. published evidence in Nature Neuroscience for the lasting epigenetic impact of maternal care within the hippocampus of rat offspring. This conceptual and methodological leap contributed to the evolution of environmental and behavioral epigenetics and continues to inspire challenging questions about genes, environments, and their legacy.

Cts of prenatal exposure of 850-1900MHz mobile phone on the expression of PCNA and DCX in dentate gyrus of offspring rats

To evaluate the effect of prenatal mobile phone exposure on the expression of proliferating cell nuclear antigen (PCNA) and doublecortin (DCX) in dentate gyrus of offspring rats. The rat model of prenatal mobile phone exposure was established and there were three groups including control group, short term maternal exposure group and long term maternal exposure group(n=6). From pregnant day 1 to day 17, pregnant rats in long term and short term maternal exposure group were exposed to an mobile phone in talking mode for 6 h/d and 24 h/d, respectively. Length of pregnancy, maternal body weight gain, litter size and pup's body weight were observed. The cell morphology in dentate gyrus of offspring rats at the age of 1 month was studied by cresyl violet staining. The immunohistochemical expression of PCNA and DCX in dentate gyrus of rat offspring were detected, and the expression of DCX and brain derived neurotrophic factor (BDNF) in hippocampus of rat offspring were evaluated by Western blot. There was no difference in length of pregnancy, maternal body weight gain, litter size and pup's body weight among three groups. The morphological changes of pyramidal cells in the polymorphic layer and DCX-positive cells in the dentate gyrus were obvious in rat offspring of long term maternal exposure group. There were less PCNA-positive cells in dentate gyrus and decreased expression of DCX and BDNF in hippocampus by Western blot in long term maternal exposure group compared with control and short term maternal exposure group (all P<0.05). Long term prenatal mobile phone exposure might inhibit the expression of PCNA and DCX in dentate gyrus of rat offspring by down-regulating BDNF.

The effect of methamphetamine exposure during pregnancy and lactation on hippocampal doublecortin expression, learning and memory of rat offspring.

The aim of this study was to evaluate the effect of methamphetamine (MA) exposure during pregnancy and lactation on doublecortin (DCX) expression in the hippocampus of rat offspring and also on learning/memory. Thirty-five pregnant Wistar rats were randomly divided into seven groups of 5 rats each: three experimental groups, each receiving 5mg/kg body weight (BW) intraperitoneal (i.p.) injections of MA during pregnancy or/and lactation; three sham groups, each receiving saline injections; one control group, receiving no injection. After the interventions, two male pups (1 and 22 days old) were randomly selected from each mother, sacrificed and their brains subjected to DCX immunohistochemistry. One additional male pup from each mother was randomly selected and maintained for 60days for testing in the Morris water maze and passive avoidance tests. MA administration during pregnancy was found to have significantly decreased the number of DCX-positive cells in the CA1, CA3 and DG regions of the hippocampus in the 1-day pups (P≤0.05) and to have significantly decreased the number of DCX-positive cells in only two regions of the hippocampus, the CA1 and DG regions, in 22-day old pups. In comparison, exposure to MA during lactation was only associated with a significant decrease in the number of DCX-positive cells in the DG. Exposure to MA during pregnancy had significant impact on the intensity of DCX expression in the hippocampus of 1- and 22-day pups (P≤0.05). There was no significant difference in memory/learning among the study groups. Our results indicate the administration of MA during pregnancy had a greater effect that during the lactation period on DCX expression in the hippocampus of rat offspring.

Effect of methamphetamine exposure during pregnancy and lactation on polysialic acid-neural cell adhesion molecule expression in rat's offspring hippocampus.

Pregnant women constitute about half the users of methamphetamine (MA), in whom the consumption may continue during breastfeeding. This study aimed to evaluate the effects of MA use during pregnancy and lactation on the hippocampus of pups. 35 pregnant Wistar rats were divided into seven groups, including three experimental groups daily administered with 5mg/kg of MA (i.p.) during the prenatal and/or postnatal period (PND1-22). In addition, three sham control groups received normal saline at the same dose, and one normal control group received no interventions since early pregnancy until the end of lactation. After the interventions, two pups (aged one and 22days) were randomly selected from each mother and their brain tissue sections were prepared to determine the expression of PSA-NCAM molecules and sialic acids using immunohistochemical and lectinhistochemical techniques, respectively. In one-day infant rats with MA exposure during pregnancy, a significant decrease was observed in the number of PSA-NCAM positive cells in the CA1 (P=0.047), CA3 (P=0.05) and DG (P=0.006) hippocampus regions compared to control and expression intensity of these molecules in all the three regions (P≤0.05). Moreover, in 22-day pups with MA exposure during pregnancy and lactation, number of PSA-NCAM positive cells and expression intensity of these molecules significantly reduced in all the three regions of the hippocampus (P≤0.05). Findings regarding the intensity of sialic acid expression were aligned with PSA-NCAM expression. According to our results, MA administration during pregnancy and lactation may effect on polysialic acid-neural cell adhesion molecule expression in rat's offspring hippocampus.

Maternal exposure to titanium dioxide nanoparticles during pregnancy and lactation alters offspring hippocampal mRNA BAX and Bcl-2 levels, induces apoptosis and decreases neurogenesis

IntroductionThe usage of Titanium dioxide nanoparticles (TiO2-NPs) covers a vast area in different fields ranging from cosmetics and food to the production of drugs. Maternal exposure to TiO2-NPs during developmental period has been associated with hippocampal injury and with a decrease in learning and memory status of the offspring. However, little is known about its injury mechanism. This paper describes the in vivo neurotoxic effects of TiO2-NPs on rat offspring hippocampus during developmental period. Material and methodsPregnant and lactating Wistar rats received intragastric TiO2-NPs (100mg/kg body weight) daily from gestational day (GD) 2 to (GD) 21 and postnatal day (PD) 2 to (PD) 21 respectively. Animals in the control groups received an equal volume of distilled water via gavage.At the end of the treatment process, offspring were deeply anesthetized and sacrificed. Then brains of each group were collected and sections of the rat offspring’s brains were stained using TUNEL staining (for detection of apoptotic cells) and immunostaining (for neurogenesis). Moreover, the right hippocampus (n=6 per each group) were removed from the right hemisphere for evaluating the expression of Bax and Bcl-2 level. ResultsResults of histopatological examination by TUNEL staining showed that maternal exposure to TiO2-NPs during pregnancy and lactation periods increased apoptotic cells significantly (P<0.01) in the offspring hippocampus. The immunolabeling of double cortin (DCX) protein as neurogenesis marker also showed that TiO2-NPs reduced neurogenesis in the hippocampus of the offspring (P<0.05). Moreover, in comparison with the control group, the mRNA levels of Bax and Bcl-2 in the TiO2-NPs group significantly increased and decreased, respectively (P<0.01). ConclusionThese findings provide strong evidence that maternal exposure to TiO2-NPs significantly impact hippocampal neurogenesis and apoptosis in the offspring. The potential impact of nanoparticle exposure for millions of pregnant mothers and their offspring across the world is potentially devastating.

Effect of lipopolysaccharide-mediated infection during pregnancy on the expression of mineralocorticoid receptor and dendritic spines in hippocampus of rat offspring

Objective To observe the effect of lipopolysaccharide (LPS)-mediated infection during pregnancy on the expression of mineralocorticoid receptor (MR) and density of dendritic spines in CA1 region of the dorsal hippocampus of rat offspring, so as to explore the mechanisms for learning and memory injury of rat offspring which were infected during prenatal period, then to provide scientific experimental evidence for the prevention of prenatal infection-induced delayed neuropsychiatric sequelae which contributed to learning and memory dysfunction. Methods Ten-week-old female Sprague-Dawley rats (n=30) were matched with male rats (11). Pregnant rats were randomly divided into a control group (n=10) and an experimental group (n=20). The pregnant rats in experimental group were treated with LPS (66 μg/kg, intraperitoneally), and the pregnant rats in control group were intraperitoneally injected with same volume of saline on gestational day 10.On postnatal day 48, Morris water maze was used to estimate the ability of learning and memory; the brain tissues of offspring were taken and paraffin sections were stained with hemato-xylin eosin (HE) for histological observation of CA1 region of the dorsal hippocampus; frozen sections were treated with indirect immunofluorescence to observe the expression of MR in CA1 region of the dorsal hippocampus; Golgi-Cox method was used to observe the density of dendritic spines of CA1 region. Results In Morris water maze test, from the third day the time of escape latency in experimental group [the 3rd day: (42.603±9.837) s; the 4th day: (30.222±9.789) s; the 5th day: (28.808±12.526) s] was significantly higher than that of the control group [the 3rd day: (28.078±14.088) s; the 4th day: (20.692±13.099) s; the 5th day: (14.632±11.624) s] (the 3rd day: t=-3.274, P<0.01; the 4th day: t=-2.257, P<0.05; the 5th day: t=-3.213, P<0.01); the swimming time in the target quadrant [(14.660±7.337) times] and the number of crossing platform [(0.933±0.704) times] in experimental group were significantly decreased compared with those of the control group [time: (23.820±6.321) s; numbers: (2.000±0.756) times](t=3.663, 4.000, all P<0.01). Hematoxylin eosin staining showed that the nerve cells of the hippocampus in the control group distributed in order, nucleuses were round or oval, nucleoli were obvious, and chromatins were homogeneous; but the cells in the experimental group distributed in disorder and pathological changes were detected, such as cellular swelling, necrosis and obvious nuclear pyknosis.By immunofluorescence staining, the average optical density (AOD) of MR in CA1 region decreased significantly in the experimental group (0.067±0.017) compared with that of the control group (0.083±0.009)(t=2.644, P<0.05). In Golgi-Cox method, the density of dendritic spines in experimental group [(7.705±0.791)/10 μm] was below that of the control group [(9.655±1.391)/10 μm](t=3.852, P<0.01). Conclusions LPS-mediated infection during pregnancy might lead to hippocampus-dependent learning and memory dysfunction which might be associated with the reduced expression of MR and the low density of dendritic spines in CA1 region of the dorsal hippocampus. Key words: Lipopolysaccharide; Hippocampus; Mineralocorticoid receptor; Dendritic spine

Propofol exposure during late stages of pregnancy impairs learning and memory in rat offspring via the BDNF-TrkB signalling pathway.

The brain‐derived neurotrophic factor (BDNF)‐tyrosine kinase B (TrkB) (BDNF‐TrkB) signalling pathway plays a crucial role in regulating learning and memory. Synaptophysin provides the structural basis for synaptic plasticity and depends on BDNF processing and subsequent TrkB signalling. Our previous studies demonstrated that maternal exposure to propofol during late stages of pregnancy impaired learning and memory in rat offspring. The purpose of this study is to investigate whether the BDNF‐TrkB signalling pathway is involved in propofol‐induced learning and memory impairments. Propofol was intravenously infused into pregnant rats for 4 hrs on gestational day 18 (E18). Thirty days after birth, learning and memory of offspring was assessed by the Morris water maze (MWM) test. After the MWM test, BDNF and TrkB transcript and protein levels were measured in rat offspring hippocampus tissues using real‐time PCR (RT‐PCR) and immunohistochemistry (IHC), respectively. The levels of phosphorylated‐TrkB (phospho‐TrkB) and synaptophysin were measured by western blot. It was discovered that maternal exposure to propofol on day E18 impaired spatial learning and memory of rat offspring, decreased mRNA and protein levels of BDNF and TrkB, and decreased the levels of both phospho‐TrkB and synaptophysin in the hippocampus. Furthermore, the TrkB agonist 7,8‐dihydroxyflavone (7,8‐DHF) reversed all of the observed changes. Treatment with 7,8‐DHF had no significant effects on the offspring that were not exposed to propofol. The results herein indicate that maternal exposure to propofol during the late stages of pregnancy impairs spatial learning and memory of offspring by disturbing the BDNF‐TrkB signalling pathway. The TrkB agonist 7,8‐DHF might be a potential therapy for learning and memory impairments induced by maternal propofol exposure.

Diabetes during pregnancy enhanced neuronal death in the hippocampus of rat offspring

BackgroundDiabetes in pregnancy has a detrimental effect on central nervous system (CNS) development and is associated with an increased risk of short- and long-term neurocognitive impairment in the offspring. This study aimed to investigate the effect of maternal diabetes and also insulin treatment on the numerical density of apoptotic cells in rat neonate’s hippocampi during the first two postnatal weeks. MethodsWistar female rats were maintained diabetic from a week before gestation through parturition and their male pup’s brains were collected at postnatal days (P); P0, P7 and P14, equivalent to the third trimester in human. Numerical density of total neurons and percentage of apoptotic (TUNEL-positive) cells in different subfields of hippocampus (CA1, CA2, CA3, and DG) was calculated by stereological methods. ResultsImmediately after birth, we found a significantly decline in the total neuronal density only in hippocampal CA3 area in neonates born to diabetic animals (p<0.0001). Moreover, the number of neurons was significantly decreased in all hippocampal sub-regions of diabetic group pups when compared to control and insulin treated diabetic pups at both P7 and P14 (p<0.0001 each). Nevertheless, in diabetic group, the percentage of apoptotic cells in different subfields of hippocampus were higher in all studied time-points compared to control or insulin treated diabetic groups (p<0.0001 each). There were no significant differences either in the total number or apoptotic cells in the different hippocampal sub-fields between the insulin-treated diabetic group and controls (p>0.05). ConclusionOur data indicate that diabetes in pregnancy induce the neuronal cell apoptosis in offspring hippocampus. Furthermore, the maternal glycaemia control by insulin treatment in the most cases normalized these effects.

Effects of maternal enflurane exposure on NR2B expression in the hippocampus of their offspring

This work aims to study the pathogenesis of learning and memory impairment in offspring rats resulting from maternal enflurane anesthesia by focusing on the expression of the N-methyl-d-aspartic acid receptor subunit 2B (NR2B) in the hippocampus of the offspring. Thirty female Sprague-Dawley rats were randomly divided into three groups: control (C group), 4 h enflurane exposure (E1 group), and 8 h enflurane exposure (E2 group) groups. Eight to ten days after the initiation of pregnancy, rats from the E1 and E2 groups were allowed to inhale 1.7% enflurane in 2 L/min oxygen for 4 h and 8 h, respectively. Rats from the C group were allowed to inhale 2 L/min of oxygen only. The Morris water maze was used to assay the learning and memory function of the offspring on postnatal days 20 and 30. RT-PCR and immunohistochemistry assays were then used to measure the mRNA levels and protein expression of NR2B, respectively. Relative to offspring rats from the C group, those from the E1 and E2 groups exhibited longer escape latencies, lesser number of crossings over the platform, and less time spent in the target quadrant in the spatial exploration test (P &lt; 0.05). In addition, the mRNA and protein expression levels of NR2B in the hippocampus of offspring rats in the E1 and E2 groups were down-regulated (P &lt; 0.05). No significant differences between the E1 and E2 groups were observed (P &gt; 0.05) in terms of mRNA levels and protein expression of NR2B. The cognitive function of the offspring is impaired when maternal rats are exposed to enflurane during early pregnancy. A possible mechanism of this effect is related to the down-regulation of NR2B expression.

Effects of nano-lead exposure on learning and memory as well as iron homeostasis in brain of offspring rats

To investigate the effects of nano-lead exposure on learning and memory and iron homeostasis in the brain of the offspring rats on postnatal day 21 (PND21) and postnatal day 42 (PND42). Twenty adult pregnant female Sprague-Dawley rats were randomly divided into control group and nano-lead group. Rats in the nano-lead group were orally administrated 10 mg/kg nano-lead, while rats in the control group were administrated an equal volume of normal saline until PND21. On PND21, the offspring rats were weaned and given the same treatment as the pregnant rats until 42 days after birth. The learning and memory ability of offspring rats on PND21 and PND42 was evaluated by Morris water maze test. The hippocampus and cortex s amples of offspring rats on PND21 and PND42 were collected to determine iron and lead levels in the hippocampus and cortex by inductively coupled plasma-mass spectrometry. The distributions of iron in the hippocampus and cortex were observed by Perl's iron staining. The expression levels of ferritin, ferroportin 1 (FPN1), hephaestin (HP), and ceruloplasmin (CP) were measured by enzyme-linked immunosorbent assay. After nano-lead exposure, the iron content in the cortex of offspring rats on PND21 and PND42 in the nano-lead group was significantly higher than those in the control group (32.63 ± 6.03 µg/g vs 27.04 ± 5.82 µg/g, P<0.05; 46.20 ±10.60 µg/g vs 36.61 ± 10.2µg/g, P<0.05). The iron content in the hippocampus of offspring rats on PND42 in the nano-lead group was significantly higher than that in the control group (56.9 ± 4.37µg/g vs 37.71 ± 6.92µg/g, P<0.05). The Perl's staining showed massive iron deposition in the cortex and hippocampus in the nano-lead group. FPNl level in the cotfex of offspring rats on PND21 in the nano-lead group was significantly lower than that in the control group (3.64 ± 0.23 ng/g vs 4.99 ± 0.95 ng/g, P<0.05). FPN1 level in the hippocampus of offspring rats on PND42 in the nano-lead group was significantly lower than that in the control group (2.28 ± 0.51 ng/g vs 3.69 ± 0.69 ng/g, P<0.05). The escape latencies of offspring rats on PND21 and PND42 in the nano-lead group were longer than those in the control group (15.54 ± 2.89 s vs 9.01 ± 4.66 s; 6.16 ± 1.42 s vs 4.26 ± 1.51 s). The numbers of platform crossings of offspring rats on PND21 and PND42 in the nano- lead group were significantly lower than those in the control group (7.77 ± 2.16 times vs 11.2 ± 1.61 times, P<0.05; 8.12 ± 1.51 times vs 13.0 ± 2.21 times, P<0.05). n Nano-lead exposure can result in iron homeostasis disorders in the hippocampus and cortex of offspring rats and affect their learning and memory ability.

Perfluorooctane sulfonate induces apoptosis of hippocampal neurons in rat offspring associated with calcium overload

The purpose of this research is to investigate the effects of perfluorooctane sulfonate (PFOS) on neuronal apoptosis in the hippocampus of rat offspring, and to elucidate the underlying mechanisms associated with calcium homeostasis.

Effect of prenatal exposure to LPS combined with pre- and post-natal high-fat diet on hippocampus in rat offspring

ObjectivePrenatal exposure to lipopolysaccharide (LPS) or high-fat diet (HFD) results in hippocampal impairment and cognitive deficits in offspring rats. What is not clear is how prenatal exposure to LPS combined with pre- and post-natal HFD would affect the hippocampus in offspring rats. Methods32 pregnant rats were randomly divided into four groups, including control group; LPS group (pregnant rats were injected with LPS 0.4mg/kg intraperitoneally on the 8th, 10th and 12th day of pregnancy); HFD group (maternal rats had HFD during pregnancy and the lactation period, and their pups also had HFD up to the third month of life); LPS+HFD group (rats were exposed to the identical experimental scheme with LPS group and HFD group). The serum IL-6 and TNF-alpha concentration was measured in three-month-old offspring rats in all groups. Hippocampal morphology and expressions of glial fibrillary acidic protein (GFAP), Tau and synaptophysin (SYP) in offspring rats were measured. ResultsSerum IL-6 and TNF-alpha concentration in the HFD group increased significantly compared with the control group, LPS group and LPS+HFD group. Compared with the control group and the LPS+HFD group, cells in the LPS and HFD groups were smaller and arranged in disorder, and cell membrane was not complete, nucleoli and nuclear heterochromatin stained darkly with hematoxylin. GFAP and Tau expression in the hippocampus of the LPS and HFD groups increased significantly compared with the control group and LPS+HFD group. SYP expression in the LPS and HFD groups decreased significantly compared with the control group and HFD group, increased in the LPS+HFD group. ConclusionPrenatal exposure to LPS combined with pre- and post-natal HFD result in a protective effect on the hippocampus in offspring rats, and it might be a benefit from the predictive adaptive response to prenatal inflammation.

The effects of nano-silver and garlic administration during pregnancy on neuron apoptosis in rat offspring hippocampus.

The aim of this study was to investigate the effects of nano-silver and garlic administration during pregnancy on neuron apoptosis in rat offspring hippocampus. FIFTY PREGNANT WISTAR RATS WERE RANDOMLY DIVIDED INTO FIVE GROUPS: 1- nano-silver (N.S) group; 30 mg/kg of N.S treated via gavage. 2- Control (C) group, administrated with distilled water via gavage. 3- N.S and garlic (N.S+G) group; N.S (30 mg/kg) and garlic juice (1 ml/100 g) treated via gavage simultaneously. 4- Garlic group (G); garlic juice (1 ml/100 g) administrated via gavage, 5- normal (N) without any intervention. All the interventions were done during pregnancy (21 days). Finally, the brains of rat offspring were removed to use for nano-silver level measurement and TUNEL staining. The mean of TUNEL positive cell numbers per unit area (NA) in different regions of hippocampus were compared in all animal groups. The results revealed a significant increase of hippocampus nano-silver level in N.S and N.S+G groups comparing to N group (P<0.05) and a significant decrease in nano-silver level in N.S+G group comparing to N.S group (P<0.01). The number of TUNEL positive cells in the CA1, CA3, and DG fields of rat offspring hippocampus increased in N.S and N.S+G groups comparing to other ones, and also reduced significantly in N.S+G group comparing to N.S group ((¥) P< 0.01). Our results showed that co-administration of nano-silver and garlic during pregnancy may lead to reduce nano-silver induced apoptotic cells in their offspring hippocampus.

Expression of neurogranin in hippocampus of rat offspring exposed to restraint stress and pulsed magnetic fields

Stressor acting upon the organism during pregnancy can produce distinct and long lasting effects on the offspring. However, the essential mechanism remains unclear. Neurogranin (Ng) is a postsynaptic brain-specific protein involved in the regulation of calcium signaling and neuronal plasticity. Our purpose was to investigate whether Ng plays a regulating role in the effects of prenatal restraint stress (PS) and prenatal pulsed magnetic fields (PMFs) on the hippocampus of rat offspring. Sprague Dawley female rats at gestational days 14–20 were given restraint stress or pulsed magnetic fields. The male and female offspring rats were sacrificed at the age of 1 month. The expression of Ng in the offspring hippocampus was determined using immunohistochemistry and western blotting. The results showed that PS induces a significantly inhibitory effect on the expression of Ng, especially in female offspring. The 0.11T of prenatal PMFs could increase the expression of Ng in offspring hippocampus. There was no significant difference between female and male offspring in PMFs group. The prenatal restraint stress-induced decrease in Ng expression in offspring hippocampus might be associated with the deficit in spatial learning and memory reported previously. The 0.11T of prenatal PMFs induced a significant stimulatory effect on protein expression of Ng. It was believed that PMFs stress might enhance the synaptic growth and remodeling.

Impact of Perinatal Systemic Hypoxic–Ischemic Injury on the Brain of Male Offspring Rats: An Improved Model of Neonatal Hypoxic–Ischemic Encephalopathy in Early Preterm Newborns

In this study, we attempted to design a model using Sprague-Dawley rats to better reproduce perinatal systemic hypoxic-ischemic encephalopathy (HIE) in early preterm newborns. On day 21 of gestation, the uterus of pregnant rats were exposed and the blood supply to the fetuses of neonatal HIE groups were thoroughly abscised by hemostatic clamp for 5, 10 or 15 min. Thereafter, fetuses were moved from the uterus and manually stimulated to initiate breathing in an incubator at 37 °C for 1 hr in air. We showed that survival rates of offspring rats were decreased with longer hypoxic time. TUNEL staining showed that apoptotic cells were significant increased in the brains of offspring rats from the 10 min and 15 min HIE groups as compared to the offspring rats in the control group at postnatal day (PND) 1, but there was no statistical difference between the offspring rats in the 5 min HIE and control groups. The perinatal hypoxic treatment resulted in decreased neurons and increased cleaved caspase-3 protein levels in the offspring rats from all HIE groups at PND 1. Platform crossing times and the percentage of the time spent in the target quadrant of Morris Water Maze test were significantly reduced in the offspring rats of all HIE groups at PND 30, which were associated with decreased brain-derived neurotrophic factor levels and neuronal cells in the hippocampus of offspring rats at PND 35. These data demonstrated that perinatal ischemic injury led to the death of neuronal cells and long-lasting impairment of memory. This model reproduced hypoxic ischemic encephalopathy in early preterm newborns and may be appropriate for investigating therapeutic interventions.

Maternal and early life arsenite exposure impairs neurodevelopment and increases the expression of PSA-NCAM in hippocampus of rat offspring

Although epidemiological investigations indicate that chronic arsenic exposure can induce developmental neurotoxicity in children, the molecular mechanisms are still poorly understood. Neural cell adhesion molecules (NCAMs) play critical roles during the development of nervous system. Polysialylation of NCAM (PSA-NCAM) is a critical functional feature of NCAM-mediated cell interactions and functions. The present study aimed at investigating the effects of maternal and early life arsenite exposure on NCAM and PSA-NCAM in rat offspring. To this end, mother rats were divided into three groups and exposed to 0, 2.72 and 13.6mg/L sodium arsenite, respectively, during gestation and lactation. After weaning, rat offspring drank the same solution as their mothers. Neural reflex parameters, arsenic level of hippocampus, ultra-structural changes of hippocampus, the expression of NCAM, PSA-NCAM and two polysialyltransferases (STX and PST) in rat offspring were assessed. Arsenite exposure significantly prolonged the time of completing reflex response of surface righting, negative geotaxis and cliff avoidance of rat offspring in 13.6mg/L As-exposed group. Neurons and capillaries presented pathological changes and the expression of NCAM, PSA-NCAM, STX and PST were up-regulated in hippocampus of rat offspring exposed to arsenite. These results indicated that maternal arsenite exposure increases the expression of PSA-NCAM, NCAM and polysialyltransferases in hippocampus of rat offspring on postnatal day (PND) 21 and PND120, which might contribute to the impaired neurodevelopment following arsenite exposure.