Behavior Of Rat Offspring Research Articles

Caffeine intake during lactation has a sex-dependent effect on the hippocampal excitatory/inhibitory balance and pups’ behavior

During early life, disruptions in glutamatergic and GABAergic synapse development in the hippocampus may contribute to several neurodevelopmental disorders, including cognitive deficits and psychiatric disorders. Caffeine is the most consumed psychoactive drug in the world, and previous work from our group has shown that caffeine disrupts visual system connections at different stages of development. This work aimed to investigate the effects of caffeine consumption during lactation in the glutamatergic and GABAergic synaptic markers in the hippocampus and on the behavior of rat offspring. We found that maternal caffeine intake significantly reduced GluN1 subunits of the NMDA receptor, increased the GluA1/GluA2 ratio of AMPA receptor in the dorsal hippocampus, and decreased GAD content in female pups’ ventral hippocampus. On the other hand, an increase in GluN1/GluN2b subunits, a decrease in GAD content in the dorsal hippocampus, and a reduction of the GluA1 content in the ventral hippocampus were observed in male pups. In addition, changes in the behavior of the offspring submitted to indirect caffeine consumption were also sex-dependent, with females developing anxiety-like behavior and males showing anxiety-like behavior and hyper-locomotion. These results highlight that maternal caffeine intake promotes changes in the hippocampal excitatory and inhibitory balance and offspring behavior in a sex-dependent manner, suggesting that the population should be alerted to reduced caffeine consumption by breastfeeding mothers.

Combined Effect of Maternal Separation and Early-Life Immune Activation on Brain and Behaviour of Rat Offspring.

Adversity during early life, a critical period for brain development, increases vulnerability and can have a lasting impact on the brain and behaviour of a child. However, the long-term effects of cumulative early-life stressors on brain and behaviour are not well known. We studied a 2-hit rat model of early-life adversity using maternal separation (MS) and immune activation (lipopolysaccharide (LPS)). Rat pups underwent MS for 15 (control) or 180 (MS) minutes per day from postnatal day (P)2-14 and were administered saline or LPS (intraperitoneal) on P3. Open-field (OFT) and object-place recognition tests were performed on rat offspring at P33-35 and P42-50, respectively. The pre-frontal cortex (PFC) and hippocampus were removed at the experimental endpoint (P52-55) for mRNA expression. MS induced anxiety-like behaviour in OFT in male and reduced locomotor activity in both male and female offspring. LPS induced a subtle decline in memory in the object-place recognition test in male offspring. MS increased glial fibrillary acidic protein (GFAP) and brain-derived neurotrophic factor expression in PFC and ionised calcium-binding adapter molecule-1 expression in male hippocampus. MS and LPS resulted in distinct behavioural phenotypes in a sex-specific manner. The combination of MS and LPS had a synergistic effect on the anxiety-like behaviour, locomotor activity, and GFAP mRNA expression outcomes.

Maternal rat prenatal and neonatal treatment with pequi pulp reduces anxiety and lipid peroxidation in brain tissue of rat offspring at adolescence

The Pequi fruit (Caryocar Brasiliense cambess), typical of the Brazilian cerrado or savannah, is a source of essential fatty acids, carotenoids, and phenolic compounds. The aim of this study was to analyze the effects of consuming this fruit on anxiety behavior and lipid peroxidation in the brains of rats whose mothers were treated (by gavage) during pregnancy and lactation with Pequi fruit (pulp or nuts) at 2000 mg/kg of body weight. Anxiety parameters were assessed using the open field (OF), elevated plus maze (EPM), and light/dark box (LDB) tests. The brain was removed to measure malondialdehyde (MDA) levels. Data were analyzed using One-way Anova (p < 0.05). In the OF, the animals in the pulp group presented more time spent in the central area (20.37 ± 0.73 vs Control: 12.51 ± 0.39; Nuts: 8.28 ± 0.40) and increased locomotion (159.7 ± 6.10) compared to the other groups (Control: 127.3 ± 5.54; Nuts: 139.08 ± 6.57). In the EPM, the pulp group entered into the open arms (8.57 ± 0.36) and stayed more time in the central area (19.44 ± 1.17) compared to the Nuts group (7.14 ± 0.34; 13.00 ± 1.57). In the LDB the pulp group entered more (8.00 ± 0.42 vs Control: 7.16 ± 0.16 and Nuts: 7.42 ± 0.75) and stayed longer in the clear light side (92.18 ± 6.42) than all the other groups (Control: 71.44 ± 3.53; Nuts: 80.57 ± 6.50), respectively. Pulp group presented lower MDA in the brain (55.34 ± 3.04) compared to Control (72.06 ± 4.66) and Nuts (66.57 ± 2.45). We conclude that Pequi pulp consumption during pregnancy and lactation reduces lipid peroxidation in brain tissue and induces anxiolytic-like behavior in rat offspring. These effects were not observed in the Pequi nuts group.

Progressive disruption of neurodevelopment by mid-gestation exposure to lipopolysaccharides and the ameliorating effect of continuous alpha-glycosyl isoquercitrin treatment.

We investigated the effect of lipopolysaccharide (LPS)-induced maternal immune activation used as a model for producing neurodevelopmental disorders on hippocampal neurogenesis and behaviors in rat offspring by exploring the antioxidant effects of alpha-glycosyl isoquercitrin (AGIQ). Pregnant Sprague-Dawley rats were intraperitoneally injected with LPS (50 μg/kg body weight) at gestational days 15 and 16. AGIQ was administered in the diet to dams at 0.5% (w/w) from gestational day 10 until weaning at postnatal day 21 and then to offspring until adulthood at postnatal day 77. During postnatal life, offspring of LPS-injected animals did not show neuroinflammation or oxidative stress in the brain. At weaning, LPS decreased the numbers of type-2b neural progenitor cells (NPCs) and PCNA+ proliferating cells in the subgranular zone, FOS-expressing granule cells, and GAD67+ hilar interneurons in the dentate gyrus. In adulthood, LPS decreased type-1 neural stem cells, type-2a NPCs, and GAD67+ hilar interneurons, and downregulated Dpysl3, Sst, Fos, Mapk1, Mapk3, Grin2a, Grin2b, Bdnf, and Ntrk2. In adults, LPS suppressed locomotor activity in the open field test and suppressed fear memory acquisition and fear extinction learning in the contextual fear conditioning test. These results indicate that mid-gestation LPS injections disrupt programming of normal neurodevelopment resulting in progressive suppression of hippocampal neurogenesis and synaptic plasticity of newborn granule cells by suppressing GABAergic and glutamatergic neurotransmitter signals and BDNF/TrkB signaling to result in adult-stage behavioral deficits. AGIQ ameliorated most aberrations in hippocampal neurogenesis and synaptic plasticity, as well as behavioral deficits. Effective amelioration by continuous AGIQ treatment starting before LPS injections may reflect both anti-inflammatory and anti-oxidative stress effects during gestation and neuroprotective effects of continuous exposure through adulthood.

Effects of RhoA on depression-like behavior in prenatally stressed offspring rats

Depression is a common mental disease that can lead to suicide when severe. Exposure to prenatal stress (PS) can lead to depression-like behavior in offspring, but the mechanism is unclear. RhoA (Ras homology family member A) plays an important role in stress-induced changes in synaptic plasticity, participating in the development of depression by activating the downstream effector ROCK (Rho-associated protein kinase). This study explored the influence in the expression of RhoA and downstream molecules ROCK1/2 in prenatally stressed rats, and the effect of RhoA inhibitor simvastatin on depression-like behavior induced by PS. Depression-like behavior in offspring was detected by sucrose preference test, forced swimming test, and open-field test. The mRNA and protein expression of RhoA and ROCK1/2 in the hippocampus and prefrontal cortex of offspring rats were detected by qRT-PCR and western blotting, respectively. Our results showed that PS causes depression-like behavior in offspring rats, associated with elevated expression of RhoA, ROCK1/2 in the hippocampus and prefrontal cortex. After administration of simvastatin to PS rats, the expression of RhoA and ROCK2 was significantly reduced, alleviating depression-like behavior. Our study demonstrated that RhoA participates in the depression-like behavior in prenatally stressed offspring rats, which may be a potential target for antidepressant therapy.

Evaluation of p21 expression and related autism-like behavior in Bisphenol-A exposed offspring of Wistar albino rats.

Bisphenol A (BPA), an endocrine disruptor, may be involved in the etiology of autism spectrum disorders (ASD); however, the mechanism of neuronal and astrocytic damage remains ambiguous. A possible role of altered expression of p21 in autistic-like behavior in rat offspring was examined with prenatal and postnatal BPA exposure. Wistar albino dams were exposed to BPA (5mg/kg) intraperitoneally throughout pregnancy and until the third postnatal day (PND). Pups were examined on 21st PND for behavioral test. Blood samples were collected for serum lactate levels and pups were sacrificed. Right frontal cortices were dissected out and processed for H&E, immunohistochemical analysis, and gene expression. Anxiety like behavior and thigmotaxis along with reduction in serum lactate concentrations were observed in pups exposed to BPA. Decline in neuronal number and decreased astrocytic population with reduced dendritic spines were revealed by H&E and immunohistochemical analysis, respectively, in right frontal cortices. Over expression of p21 was also detected in BPA-exposed offspring. Over expression of p21 may be associated with autistic behavior. Further studies are recommended to explore the structural alterations in other white matter pathways in frontal cortices.

Effects of high-fat diet on growth and depression-like behavior of prenatal stress offspring rats

To investigate effects of high-fat diet (HFD) on body length, weight and depression-like behavior of prenatal stress (PS) offspring rats. PS rat model was established by restraint stress. Sucrose preference and forced swimming tests were performed. Moreover, the effects of HFD on the growth and depression-like behavior in offspring rats were observed. Length of male and female HF group was significantly longer than that control, but length of male PS+HF group was significantly shorter than HF group. Body weight of male and female HF group was significantly higher than control, and body weight of male PS+HF group was significantly lower than HF group. No significant differences were observed in length between female PS +HF and HF groups. Compared with male PS+HF group, growth rate of male HF group was significantly higher. Moreover, HFD could reduce sucrose preference, and prolong immobility time of PS offspring rats. HFD can promote weight gain of male and female normal offspring rats. PS can partially inhibit effects of HFD on weight gain of PS male offspring rats, but exert no significant effects on PS female offspring rats. HFD can aggravate PS-induced depression-like behavior in offspring rats.

Converging Effects of Three Different Endocrine Disrupters on Sox and Pou Gene Expression in Developing Rat Hippocampus: Possible Role of microRNA in Sex Differences.

Endocrine disrupting chemicals (EDCs) can impair hippocampus-dependent behaviors in rat offspring and in children. In search for key processes underlying this effect, we compared the transcriptomes of rat hippocampus on postnatal day 6 after gestational and lactational exposure to three different EDCs at doses known to impair development of learning and memory. Aroclor 1254, a commercial PCB mixture (5 mg/kg or 0.5 mg/kg), or bisphenol A (5 mg/kg or 0.5 mg/kg) were administered in chow, chlorpyrifos (3 mg/kg or 1 mg/kg) was injected subcutaneously. Male hippocampus exhibited a common effect of all three chemicals on genes involved in cell-autonomous processes, Sox6, Sox11, Pou2f2/Oct2, and Pou3f2/Brn2, all upregulated at the high dose. Additional genes of the Sox and Pou families were affected by only one or two of the chemicals. Real time RT PCR showed a comparable expression change for bisphenol A also at the lower dose. Female hippocampus exhibited much fewer genes with expression changes (almost none with false discovery rate <0.05), and none of the genes of the Sox and Pou families was affected. Since gene network analyses in male hippocampus suggested a link between Sox6 and miR-24, known to be repressed by activation of ER-alpha and to repress Sox6 in other tissues, this microRNA was measured. miR-24 was downregulated by all chemicals at the high dose in males. Values of Sox6 mRNA and miR-24 were inversely correlated in individual male hippocampus samples, supporting the hypothesis that the change in Sox6 expression resulted from an action of miR-24. In contrast, miR-24 levels remained unchanged in hippocampus of females. A sexually dimorphic response of miR-24 may thus be at the basis of the sex difference in Sox6 expression changes following exposure to the three chemicals. ER-alpha expression was also sex-dependent, but the expression changes did not parallel those of potential downstream genes such as Sox6. Sox6 is known to suppress differentiation of Parvalbumin (Pvalb)-expressing interneurons. Individual Sox6 levels (FPKM) were inversely correlated with levels of Pvalb, but not with markers of Sox6-independent interneuron subpopulations, Nos1 and 5HT3aR. Effects on interneuron development are further suggested, in males, by expression changes of Nrg1 and its receptor Erbb4, controlling interneuron migration. Our study disclosed new types of EDC-responsive morphogenetic genes, and illustrated the potential relevance of microRNAs in sexually dimorphic EDC actions.

Alteration of the Early Development Environment by Maternal Diet and the Occurrence of Autistic-like Phenotypes in Rat Offspring.

Epidemiological and preclinical studies suggest that maternal obesity increases the risk of autism spectrum disorder (ASD) in offspring. Here, we assessed the effects of exposure to modified maternal diets limited to pregnancy and lactation on brain development and behavior in rat offspring of both sexes. Among the studied diets, a maternal high-fat diet (HFD) disturbed the expression of ASD-related genes (Cacna1d, Nlgn3, and Shank1) and proteins (SHANK1 and TAOK2) in the prefrontal cortex of male offspring during adolescence. In addition, a maternal high-fat diet induced epigenetic changes by increasing cortical global DNA methylation and the expression of miR-423 and miR-494. As well as the molecular changes, behavioral studies have shown male-specific disturbances in social interaction and an increase in repetitive behavior during adolescence. Most of the observed changes disappeared in adulthood. In conclusion, we demonstrated the contribution of a maternal HFD to the predisposition to an ASD-like phenotype in male adolescent offspring, while a protective effect occurred in females.

HIF-1 α may play a role in late pregnancy hypoxia-induced autism-like behaviors in offspring rats

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that can be caused by various factors. The present study aimed to determine whether prenatal hypoxia can lead to ASD and the role of hypoxia-inducible factor-1α (HIF-1α) in this process. We constructed a prenatal hypoxia model of pregnant rats by piping nitrogen and oxygen mixed gas, with an oxygen concentration of 10 ± 0.5 %, into the self-made hypoxia chamber. Rats were subjected to different extents of hypoxia treatments at different points during pregnancy. The results showed that hypoxia for 6 h on the 17th gestation day is most likely to lead to autistic behavior in offspring rats, including social deficits, repetitive behaviors, and impaired learning and memory. The mRNA expression level of TNF-α also increased in hypoxia-induced autism group and valproic acid (VPA) group. Western blotting analysis showed increased levels of hypoxia inducible factor 1 alpha (HIF-1α) and decreased levels of phosphatase and tensin homolog (PTEN) in the hypoxic-induced autism group. Meanwhile, N-methyl d-aspartate receptor subtype 2 (NR2A) and glutamate ionotropic receptor AMPA type subunit 2 (GluR2) were upregulated in the hypoxic-induced autism group. HIF-1α might play a role in hypoxia-caused autism-like behavior and its regulatory effect is likely to be achieved by regulating synaptic plasticity.

Disorder of intestinal amino acid pathway in depression-like offspring rats induced by maternal separation.

To investigate the intestinal amino acids pathway in depression-like offspring rats induced by maternal separation. Sprague-Dawley (SD) female rats were randomly divided into a control group (=8) and a maternal separation group (=8). After normal delivery, the maternal rats were separated from offsprings for 14 consecutive days and 3 h per day in maternal separation group; while rats in the control group was received no interventions in postpartum. Depression-like behaviors of offspring rats were evaluated using the sucrose preference test, novelty suppressed feeding test, and forced swimming test. Amino acid analyzer was used to detect the changes of amino acid contents in the small intestine, and the expressions of alanine-serine-cysteine transporter 2 (ASCT2), solute carrier superfamily 6 member 19 (BAT1) and L-type amino acid transporter 1(LAT1) were detected by Western blot. The weight of the offspring rats in the maternal separation group was significantly lower than that of the control group at 21 and 28 d (=4.925 and 5.766, all <0.01). Compared with the control group, the percentage of sucrose preference of the offspring rats in the maternal separation group was significantly reduced (=2.709, <0.05), and the feeding latency was significantly prolonged (=-13.431, <0.01). The immobility time in FST of maternal separation group was significantly longer (=-3.616, <0.01).Increased concentration of aspartic acid (=-6.672, <0.01) and down-regulation of glutamine (=3.107, <0.01) and glycine (=9.781, <0.01) were observed in maternal separation group. Western blot analysis revealed that the protein expressions of ASCT2 (=6.734, <0.01) and BAT1 (=9.015, <0.01) in maternal separation group were reduced, while the expression of LAT1 was increased (=-8.942, <0.01). Maternal separation can induce the depression-like behavior in offspring rats; the amino acid contents and the amino acid transporter expression in the small intestine are reduced, which may be related to depression-like behavior induced by maternal separation.

The Behavior and Postnatal Development in Infant and Juvenile Rats After Ultrasound-Induced Chronic Prenatal Stress.

Fetal development is susceptible to environmental factors. One such factor is exposure to stress during pregnancy. The present study aimed to investigate the effects of chronic prenatal stress (PS) on the development and behavior of rat offspring during infancy and juvenile ages. Existing approaches to modeling prenatal stress on animals do not correlate with the main type of stress in pregnant women, namely psychological stress. We used a new stress paradigm in the experiment, namely, stress induced by exposure to variable frequency ultrasound (US), which acted on pregnant Wistar rats on gestational days 1–21. This type of stress in rodents can be comparable to psychological stress in humans. We assessed physical development, reflex maturation, motor ability development, anxious behavior, response to social novelty, and social play behavior in male and female offspring. Additionally, we investigated maternal behavior and the effect of neonatal handling (NH) on behavior. Prenatal stress did not affect postnatal developmental characteristics in rat pups, but prenatally stressed rats had higher body weight in early and adult age than controls. Prenatal exposure to a stressor increased anxiety in the open-field test (OF), changed social preferences in the social novelty test (SN), and impaired social play behavior in males. Neonatal handling reduced anxiety and restored social behavior, but evoked hyperactive behavior in rat pups. Maternal behavior did not change. Our study demonstrated for the first time that exposure to variable frequency ultrasound during pregnancy influences offspring development and impairs behavior, correlating with the effects of other types of stress during pregnancy in rodents. This supports the idea of using this exposure to model prenatal stress.

Prenatal stress induced depressive-like behavior and region dependently high CRP level in offspring rats.

IntroductionTo explore the changes in C‐reactive protein (CRP) level in different regions of one old offspring rats exposed to prenatal stress (PS).MethodsThe rat model was constructed with prenatal restraint stress on pregnant dams on days 14–20 of gestation. Offspring rats were randomly divided into PS susceptibility (PS‐S) group and control (CON) group. Behavioral experiments including sucrose preference test (SPT), open‐field test (OFT), and forced swimming test (FST) were used to measure depressive‐like behaviors. Immunohistochemistry, qRT‐PCR, and Western blotting were applied to detect the changes in CRP level.ResultsThe results showed that PS could cause depressive‐like behaviors in all SPT, OFT, and FST. Concomitantly, CRP mRNA and protein expression significantly increased in hippocampus, prefrontal cortex, and hypothalamus in the PS‐S group when compared that in the CON group, while no significantly changes in liver, heart, olfactory bulb, striatum, and cerebellum in the PS‐S group when compared that in the CON group.ConclusionIncreasing of CRP expression in hippocampus, prefrontal cortex, and hypothalamus may play a critical role in the mechanism under depressive‐like behavior in offspring rats exposed to PS.

Characterization of Gut Microbiota in Prenatal Cold Stress Offspring Rats by 16S rRNA Sequencing.

Simple SummaryPrenatal stress, including prenatal cold stress has long-term effects on offspring’s physical and mental health. Our previous study showed a reduction of anxiety-like behavior in offspring rats suffered from prenatal cold stress. It is well-known that gut microbiota was involved in a variety of physiological activities, such as emotion, cognition, and behavior. However, information on the comparison between prenatal cold stress and gut microbiota in offspring is limited. The current study compared the gut microbiota composition of the prenatal cold stress and non-stress offspring rats. Cold stressed during gestation period showed to change the offspring gut microbiota composition, and Bacteroides and Lactobacillus were significantly increased in prenatal cold stress offspring rat guts. With the hope, cold stress-induced negative effects of animals can be prevented by microbiological interventions.Our previous study showed a reduction of anxiety-like behavior in offspring rats suffered from prenatal cold stress; whether this was related to changes in the offspring gut microbiota is unclear. To obtain the evidence for the role of the gut microbiota in prenatal cold stress offspring, 16S rRNA sequencing technology was used. Male and female offspring rat feces were collected from a room temperature group and a prenatal cold stress group (n ≥ 8) for microbial DNA extraction, followed by 16S rRNA sequencing. The results indicated that prenatal cold stress could change the offspring’s gut microbiota composition. Prenatal cold stress significantly upregulates Lactobacillus, Lactobacillus_gasseri, Bacteroides, and Bacteroides-acidifaciens in female offspring, whereas prenatal cold stress significantly reduced Lachnospiraceae and Prevotellaceae in male offspring. These data showed the characterization of gut microbiota in prenatal cold stress offspring rats, and these data suggest that microbiological intervention in the future can potentially prevent the negative effects caused by cold stress to animals.

Prenatal pregabalin is associated with sex-dependent alterations in some behavioral parameters in valproic acid-induced autism in rat offspring.

This study was performed to evaluate the effects of prenatal exposure to pregabalin (PGB) on behavioral changes of rat offspring in an animal model of valproic acid (VPA)-induced autism-like symptoms. Pregnant rats received VPA (600mg/kg/i.p.) once at 12.5 gestational days for autism-like symptom induction in offspring. After the delivery single male and single female offspring from each mother were randomly selected for behavioral test (anxiety, pain response, pleasure, and motor function) at 60th day adulthood (n=7). Offspring received prenatal PGB (15 & 30mg/kg/i.p.) during gestational days 9.5 to 15.5 either alone or in combination with VPA (PGB15, PGB30, PGB15+VPA, and PGB30+VPA). Control offspring received normal saline during the same period. The result showed that prenatal VPA exposure was associated with autism-like behaviors in rat offspring. PGB treatment during the gestational period revealed significant reduction in sucrose preference test and anxiety in elevated plus maze and open field test in offspring. Also, PGB treatments exhibited a dose-dependent increase in pain threshold in prenatally VPA exposed rats in tail-flick and hot plate test. Also, there was a sex-related significant impairment in motor function in beam balance and open field test, and male rats were affected more than females. However, no significant sex differences in sucrose preference and pain sensitivity were observed in prenatal PGB-treated rat offspring. In conclusion, prenatal exposure to VPA increased the risk of autism-like behaviors in the offspring rats, and PGB treatment during the gestational period was associated with some beneficial effects, including anxiety reduction and motor impairment in autism-like symptoms in rat offspring.

Perinatal fluoxetine treatment and dams’ early life stress history alter affective behavior in rat offspring depending on serotonin transporter genotype and sex

Many women diagnosed with a major depression continue or initiate antidepressant treatment during pregnancy. Both maternal stress and selective serotonin inhibitor (SSRI) antidepressant treatment during pregnancy have been associated with changes in offspring behavior, including increased anxiety and depressive-like behavior. Our aim was to investigate the effects of the SSRI fluoxetine (FLX), with and without the presence of a maternal depression, on affective behavior in male and female rat offspring. As reduced serotonin transporter (SERT) availability has been associated with altered behavioral outcome, both offspring with normal (SERT+/+) and reduced (SERT+/−) SERT expression were included. For our animal model of maternal depression, SERT+/− dams exposed to early life stress were used. Perinatal FLX treatment and early life stress in dams (ELSD) had sex- and genotype-specific effects on affective behavior in the offspring. In female offspring, perinatal FLX exposure interacted with SERT genotype to increase anxiety and depressive-like behavior in SERT+/+, but not SERT+/−, females. In male offspring, ELSD reduced anxiety and interacted with SERT genotype to decrease depressive-like behavior in SERT+/−, but not SERT+/+, males. Altogether, SERT+/+ female offspring appear to be more sensitive than SERT+/− females to the effects of perinatal FLX exposure, while SERT+/− male offspring appear more sensitive than SERT+/+ males to the effects of ELSD on affective behavior. Our data suggest a role for offspring SERT genotype and sex in FLX and ELSD-induced effects on affective behavior, thereby contributing to our understanding of the effects of perinatal SSRI treatment on offspring behavior later in life.

PDLIM5 improves depression-like behavior of prenatal stress offspring rats via methylation in male, but not female

ObjectivePrenatal stress (PS) contributes to depression-like behavior in the offspring. PDLIM5 is involved in the onset of mental disorders. This study is to investigate the role and mechanism of PDLIM5 in depression-like behavior of PS offspring rats. MethodsPS model was used to analyze the effects of different treatments to PS offspring rats with different sex, including PDLIM5, PDLIM5 shRNA and 5-aza-2’ -deoxycytidine (5-azaD). The depression-like behavior was assessed by the sucrose preference test (SPT) and forced swimming test (FST). The mRNA and protein expression levels of PDLIM5 in the hippocampus of PS offspring rats were detected by qRT-PCR and western blot, respectively. The methylation of PDLIM5 promoter were analyzed by bisulfite sequencing. ResultsOur data revealed that PS offspring rats showed a significant decrease in sucrose preference and a prolonged immobility time. Injection of PDLIM5 significantly improved the depression-like behavior in PS offspring rats, whereas administration of PDLIM5 shRNA aggravated it. In addition, PDLIM5 expression was decreased at the mRNA and protein levels, and the methylation level of PDLIM5 promoter was increased in hippocampus of PS male but not female offspring rats. Furthermore, microinjection of 5-azaD improved the PS induced depression-like behavior in offspring rats. Moreover, in male PS offspring rats, microinjection of 5-azaD reversed the effect of PS on PDLIM5 expression and promoter methylation. ConclusionPDLIM5 can significantly improve the depression-like behavior of both male and female PS offspring rats, while the PDLIM5 promoter methylation is only observed in male PS offspring rats. Our study may provide new mechanism for the pathogenesis of depression and experimental evidence for sex-based precise treatment.

Effects of Dihydroquercetin on Behavior of Albino Rat Offspring with Transgenerational Chemical Body Burden

Introduction. Lead pollution is a common environmental problem. Having no physiological functions, this toxicant has a negative polytropic impact on a body, including neurotoxic, reproductive, and transgenerational effects. The mechanism of lead toxicity is oxidative stress. Flavonoids have active antioxidant properties. They are widely represented in plant foods, are able to restore protective capabilities of cells and have chelating properties with respect to lead. One of the representatives of this group of substances is dihydroquercetin. The objective was to study the effect of dihydroquercetin on behavior of rats with hereditary chemical body burden exposed to lead at 60 mg/kg during 25 days. Materials and methods. We studied the behavior of rat offspring in an open field and established their blood lead levels by electrothermal atomization atomic absorption spectrometry. For statistical processing the U-Mann – Whitney test was used. Results. In the present experiment, the effect of lead on the offspring of male albino rats exposed to 60 mg/kg of lead for 25 days caused changes in the activity of animals in the open field. The severity of changes was more pronounced in animals with a hereditary chemical body burden. These animals showed a decrease in orientation and physical activity and increased anxiety. In rats with a hereditary burden, changes in behavior were detected when administering dihydroquercetin. The activity of animals demonstrated a positive dynamics: we observed a statistically significant increase in physical activity and orientation. The number and duration of behavioral acts approached control values. Conclusions. The revealed effects of lead on the offspring of albino rats with a transgenerational chemical body burden require further study to understand the mechanism of the phenomenon.

Effects of in utero exposure to lanthanum on neurological behavior in rat offspring

The increasing use of rare-earth elements in various fields has raised concern from public heath perspective regarding their accumulation in human body. Long-term exposure to lanthanum, one of the frequently used rare-earth elements in biomedicine and agriculture, has been previously shown to exert neurotoxicity during development in rats; however, the effects of short-term exposure to lanthanum during gestation on neurobehavioral development in rat offspring is still not clear. The purpose of this study is to investigate the effects of intrauterine exposure to lanthanum on neurobehavioral development in rat offspring. Dams were orally exposed to 0, 2, 20, & 60 mg/kg BW of lanthanum nitrate from gestation day 7 to day 16. Morris water maze test, hindlimb strength test, nociceptive perception test, and grip strength test were conducted during postnatal day 61 to 66 in rat offspring. Blood lanthanum concentration and plasma neurotransmitters were measured after sacrifice. The results showed that intrauterine exposure to lanthanum nitrate significantly impaired memory and spatial learning in Morris water maze test. Lanthanum treatment dose-dependently increased blood lanthanum concentration in dams and pups. Lanthanum treatment significantly decreased hindlimb and grip strength and increased delay time in nociceptive response. Plasma neurotransmitter results showed that lanthanum treatment significantly decreased the level of acetylcholine and serotonin while increased the level of glutamate in rat offspring. These results suggest that short-term in utero exposure to lanthanum has potential adverse effects on neurodevelopment in rat offspring.

The Impact and Mechanism of Methylated Metabotropic Glutamate Receptors 1 and 5 in the Hippocampus on Depression-Like Behavior in Prenatal Stress Offspring Rats.

An increasing number of epidemiological investigations and animal models research suggest that prenatal stress (PS) could cause depression-like behavior in the offspring, which is sex specific. However, the underlying mechanisms remain to be elucidated. This study is to investigate the promoter methylation of metabotropic glutamate receptor 1 (mGluR1) and metabotropic Glutamate Receptor 5 (mGluR5) gene modification on PS induced depression-like behavior in offspring rats (OR). PS models were established, with or without 5-aza-2′-deoxycytidine (5-azaD, decitabine) treatment. Animal behavior was assessed by the sucrose preference test (SPT), forced swimming test (FST), and open field test (OFT). The mRNA and protein expression levels of mGluR1 and mGluR5 in the hippocampus of offspring were detected with quantitative real-time PCR and Western blot analysis, respectively. The promoter methylation in the hippocampus of mGluR1 and mGluR5 OR were also analyzed. SPT showed significantly reduced sucrose preference in PS induced OR. FST showed significantly prolonged immobility time in PS induced OR. OFT showed significantly reduced central residence time in PS induced OR and no significantly influence in rearing as well as in frequency of micturition. Moreover, the mRNA, protein expression levels, and gene promoter methylation level of mGluR1 and mGluR5 in the hippocampus were significantly increased in the PS induced male OR, while no significantly influence in the PS induced female OR. Furthermore, the PS induced effects in male OR could be reversed by the microinjection of 5-azaD. In conclusion, our results showed that the promoter methylation of mGluR1 and mGluR5 gene modification is only involved in PS induced depression-like behavior in male OR in a sex-specific manner. These findings might contribute to the understanding of the disease pathogenesis and clinical treatment in future.