Male Rat Pups Research Articles

Maternal exposure to low-dose bisphenol A and its potential neurotoxic impact on male pups: A histological, immunohistochemical, and ultrastructural study

BackgroundBisphenol A (BPA) is a widely used chemical with a harmful effect on animal and human. The neonatal and juvenile period is a highly risky neurodevelopmental period. AimThis study aimed to determine how male albino rat pups’ cerebral cortex was altered by low doses of BPA given to mothers and the role of the oxidative stress. MethodsThirty pregnant rats were randomly split into three equal groups, negative control, and positive control: received 1 cc of corn oil once a day through gastric tube and BPA treated: a dose of 200 µg/kg/day (dissolved in 1 cc corn oil). The male rat pups of each group were sacrificed at 1 week, 3 weeks and 6 weeks. The cerebra were then separated from the brain for histological and biochemical studies. ResultsRats administered BPA had raised levels of lipid peroxidation marker (MDA), lower levels of enzymatic antioxidants (SOD and CAT) with decreased body, cerebral weights, and decreased levels of non-enzymatic antioxidant defense (GSH). Histo-pathologically, shrunken pyramidal cells with congested blood vessels appeared. GFAP displayed increased number of positive immune-reactive astrocytes with high statistically significant increase in the area % in BPA treated group when compared to the control groups, on contrary to MBP. Semi-thin and ultra-thin BPA-sections revealed degenerative changes in myelinated axons with tiny nucleus and broken nuclear membranes. Lysosomes, dilated endoplasmic reticulum cisternae with noticeable increase in unmyelinated nerve fibers were also observed. ConclusionThe structure of the developing cerebral cortex is negatively impacted by BPA due to oxidative stress.

Neonatal Diazepam Exposure Decreases Dendritic Arborization and Spine Density of Cortical Pyramidal Neurons in Rats.

Benzodiazepines are extensively utilized in pediatric anesthesia and critical care for their anxiolytic and sedative properties. However, preclinical studies indicate that neonatal exposure to GABAergic drugs, including benzodiazepines, leads to long-term cognitive deficits, potentially mediated by altered GABAergic signaling during brain development. This preclinical study investigated the impact of early-life diazepam exposure on cortical neuronal morphology, specifically exploring dendritic arborization and spine density, crucial factors in synaptogenesis. Male and female Sprague Dawley rat pups were exposed to a single neonatal dose of diazepam (30mg/kg) or vehicle on postnatal day (PND) 7. Golgi-Cox staining was used to assess cortical pyramidal neuron development at 4 developmental stages: neonatal (PND8), infantile (PND15), juvenile (PND30), and adolescence (PND42). Animals were randomized equally to 4 groups: male-vehicle, male-diazepam, female-vehicle, and female-diazepam. Neuronal morphology was evaluated after reconstruction in neurolucida, and dendritic spine density was analyzed through high-power photomicrographs using ImageJ. Diazepam exposure resulted in decreased dendritic complexity in both sexes, with reduced arborization and spine density observed in cortical pyramidal neurons. Significant differences were found at each developmental stage, indicating a persistent impact. Dendritic length increased with age but was attenuated by diazepam exposure. Branching length analysis revealed decreased complexity after diazepam treatment. Spine density at PND42 was significantly reduced in both apical and basal dendrites after diazepam exposure. Neonatal diazepam exposure adversely affected cortical pyramidal neuron development, leading to persistent alterations in dendritic arborization and spine density. These structural changes suggest potential risks associated with early-life diazepam exposure. Further research is needed to unravel the functional consequences of these anatomic alterations.

Effects of Memantine on Cognitive Flexibility in a Valproic Acid Rat Model of Autism

Abstract Autistic children frequently struggle with cognitive flexibility. The potential molecular mechanism underlying cognitive inflexibility remains unclear. Decreased level of brain-derived neurotrophic factor (BDNF), which plays a vital role in neural development and synaptic plasticity may have a role. This study aimed to investigate the effects of memantine on (BDNF) expression in hippocampus of prenatal VPA exposed rats, and its consequent effects on cognitive flexibility. Pregnant female rats received a single intraperitoneal injection of VPA (600 mg/kg) on gestational day 12.5 to induce autistic-like behaviors in their offspring. Afterwards, the 23-day-old male Wistar rat pups received daily intraperitoneal injections of memantine (20 mg/kg) for 4 weeks. The prenatal VPA-exposed rats exhibited reduced cognitive flexibility in the attentional set- shifting task (ASST) reflecting ASD-associated cognitive flexibility deficits, a common ASD- associated problem with accompanied reduction in hippocampal BDNF. The defective performance in ASST was more prominent in the reversal stages. Memantine associated increased hippocampal BDNF could alleviate cognitive inflexibility in ASD. This study draws attention to the potential favorable effect of memantine on cognitive performance in autistic subjects.

Early Life Stress Influences Oxidative Stress Enzyme Activities in Liver, Heart, Kidney, Suprarenal Glands, and Pancreas in Male and Female Rat Pups.

Early life stress (ELS) is a risk factor for the development of chronic diseases resulting from functional alterations of organs in the cardiorespiratory and renal systems. This work studied the changes in oxidative stress enzyme activities (EAs) of SOD, CAT, GPX, GR, GST, NOS, MDA, and FRAP in different organs (heart, liver, kidney, adrenal glands (AGs), and pancreas) of male and female Sprague-Dawley rat pups on postnatal day (PN) 15, immediately after basal and acute or chronic stress conditions were accomplished, as follows: basal control (BC; undisturbed maternal pups care), stress control (SC; 3 h maternal separation on PN15), basal maternal separation (BMS; daily 3 h maternal separation on PN 1-14), and stress maternal separation (SMS; daily 3 h maternal separation on PN 1-14 and 3 h maternal separation on PN15). Acute or long-term stress resulted in overall oxidative stress, increase in EA, and reduced antioxidant capacity in these organs. Some different response patterns, due to precedent SMS, were observed in specific organs, especially in the AGs. Acute stress exposure increases the EA, but chronic stress generates a response in the antioxidant system in some of the organs studied and is damped in response to a further challenge.

Effects of a Functional Food Made with Salvia hispanica L. (Chia Seed), Amaranthus hypochondriacus L. (Amaranth), and an Ethanolic Extract of Curcuma longa L. (Curcumin) in a Rat Model of Childhood Obesity.

Obesity is a global health problem and is increasing in prevalence in most countries. Although obesity affects all age groups, children are the most vulnerable sector. Functional foods are novel formulated foods containing substances (i.e., nutrients, phytochemicals, probiotics, etc.) that have potential health-enhancing or disease-preventing value. The research objective was to study the possible beneficial effects of providing a functional food made with amaranth flour, chia seed, and curcumin extract on the metabolism and behavior of a rat model of childhood obesity. Male Wistar rat pups from two litters of different sizes, a normal litter (NL) (10 pups) and a small litter (SL) (4 pups), were used. After weaning, the rats were fed a hypercaloric diet (HD) or an HD supplemented with the functional food mixture. Body weight and energy intake were measured for seven weeks, and locomotor activity, learning, and memory tests were also performed. At the end of the experiment, glucose and lipid metabolism parameters were determined. The results showed that in this model of obesity produced by early overfeeding and the consumption of a hypercaloric diet, anxiety-like behaviors and metabolic alterations occurred in the rat offspring; however, the provision of the functional food failed to reduce or prevent these alterations, and an exacerbation was even observed in some metabolic indicators. Interestingly, in the NL rats, the provision of the functional food produced some of the expected improvements in health, such as significant decreases in body weight gain and liver cholesterol and non-significant decreases in adipose tissue and leptin and insulin serum levels.

Sex differences in cholinergic signaling affect functional outcomes for theta-gamma coordination in hippocampal subcircuits following experimental febrile status epilepticus.

Sex determines cognitive outcome in animal models of early life seizure, where males exhibit impaired hippocampal-dependent learning and memory compared with females. The physiological underpinnings of this sex effect are unclear. Cholinergic signaling is essential for the generation of hippocampal oscillations, and supplementation of cholinergic precursors prior to status epilepticus in immature male rats prevents subsequent memory deficits. We hypothesized that there are sex differences in acetylcholine circuits and their response to experimental febrile status epilepticus (eFSE). eFSE was induced in male and female rat pups. We transversed the hippocampus of postnatal day >60 control (CTL) and eFSE rats with a 64-channel laminar silicon probe to assay cholinergic-dependent theta oscillations under urethane anesthesia. Local field potential properties were compared during (1) baseline sensory stimulation, (2) pharmacological stimulation via acetylcholine reuptake blockade, and (3) sensory stimulation after muscarinic acetylcholine receptor block (atropine). In all groups, a baseline tail pinch could elicit theta oscillations via corticohippocampal synaptic input. Following atropine, a tail pinch response could no longer be elicited in CTL male, CTL female, or eFSE female rats. In contrast, induced slow theta power in eFSE males after atropine was not decreased to spontaneous levels. Analysis of oscillation bandwidths revealed sex differences in acetylcholine modulation of theta frequency and slow gamma frequency and power. This study also identified significant effects of both sex and eFSE on baseline theta-gamma comodulation, indicating a loss of coupling in eFSE males and a potential gain of function in eFSE females. There are differences in cholinergic modulation of theta and gamma signal coordination between male and female rats. These differences may underlie worse cognitive outcomes in males following eFSE. Promoting the efficacy of muscarinic acetylcholine signaling prior to or following early life seizures could elucidate a mechanism for the temporal discoordination of neural signals within and between hippocampus and neocortex and provide a novel therapeutic approach for improving cognitive outcomes.

Sex-specific impacts of prenatal bisphenol A exposure on genes associated with cortical development, social behaviors, and autism in the offspring’s prefrontal cortex

BackgroundRecent studies have shown that prenatal BPA exposure altered the transcriptome profiles of autism-related genes in the offspring’s hippocampus, disrupting hippocampal neuritogenesis and causing male-specific deficits in learning. However, the sex differences in the effects of prenatal BPA exposure on the developing prefrontal cortex, which is another brain region highly implicated in autism spectrum disorder (ASD), have not been investigated.MethodsWe obtained transcriptome data from RNA sequencing analysis of the prefrontal cortex of male and female rat pups prenatally exposed to BPA or control and reanalyzed. BPA-responsive genes associated with cortical development and social behaviors were selected for confirmation by qRT-PCR analysis. Neuritogenesis of primary cells from the prefrontal cortex of pups prenatally exposed to BPA or control was examined. The social behaviors of the pups were assessed using the two-trial and three-chamber tests. The male-specific impact of the downregulation of a selected BPA-responsive gene (i.e., Sema5a) on cortical development in vivo was interrogated using siRNA-mediated knockdown by an in utero electroporation technique.ResultsGenes disrupted by prenatal BPA exposure were associated with ASD and showed sex-specific dysregulation. Sema5a and Slc9a9, which were involved in neuritogenesis and social behaviors, were downregulated only in males, while Anxa2 and Junb, which were also linked to neuritogenesis and social behaviors, were suppressed only in females. Neuritogenesis was increased in males and showed a strong inverse correlation with Sema5a and Slc9a9 expression levels, whereas, in the females, neuritogenesis was decreased and correlated with Anxa2 and Junb levels. The siRNA-mediated knockdown of Sema5a in males also impaired cortical development in utero. Consistent with Anxa2 and Junb downregulations, deficits in social novelty were observed only in female offspring but not in males.ConclusionThis is the first study to show that prenatal BPA exposure dysregulated the expression of ASD-related genes and functions, including cortical neuritogenesis and development and social behaviors, in a sex-dependent manner. Our findings suggest that, besides the hippocampus, BPA could also exert its adverse effects through sex-specific molecular mechanisms in the offspring’s prefrontal cortex, which in turn would lead to sex differences in ASD-related neuropathology and clinical manifestations, which deserves further investigation.

Prenatal exposure to low-dose bisphenol A disrupts hippocampal DNA methylation and demethylation in male rat offspring.

Earlier research has demonstrated that developmental exposure to bisphenol A (BPA) has persistent impacts on both adult brain growth and actions. It has been suggested that BPA might obstruct the methylation coding of the genes in the brain. In this study, the methylation changes in the hippocampus tissue of male rat pups were examined following prenatal BPA exposure. Pregnant Sprague-Dawley rats were treated with either vehicle (tocopherol-stripped corn oil) or BPA (4, 40, or 400μg/kg·body weight/day) throughout the entire duration of gestation and lactation. At 3weeks of age, the male rat offspring were euthanized, and the hippocampus were dissected out for analysis. The expression levels of DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B) and DNA demethylases (TET1, Gadd45a, Gadd45b, and Apobec1) were analyzed in the hippocampus by means of quantitative real-time polymerase chain reaction and Western blotting, respectively. The results showed that prenatal exposure to BPA upregulated the expression of enzymes associated with DNA methylation and demethylation processes in the hippocampus of male rat offspring. These findings suggest that prenatal exposure to a low dose of BPA could potentially disrupt the balance of methylation and demethylation in the hippocampus, thereby perturbing epigenetic modifications. This may represent a neurotoxicity mechanism of BPA.

Intrinsic and Extrinsic Tongue Muscles are Driven by Physiologically Distinct Motoneuron Pools

The hypoglossal motor nucleus innervates six of the seven tongue muscles responsible for wide-ranging behaviors including speech, breathing, and swallowing. Despite the task-specific nature of tongue movements, neurophysiologic research has historically treated hypoglossal motoneurons as a homogeneous population. Our previous work showed that hypoglossal motoneurons innervating specific tongue muscles had different firing thresholds and resting membrane potential. Here, we extend this work by comparing potassium conductance in motor neurons innervating the superior longitudinalis (SL; intrinsic) and genioglossus (GG; extrinsic), tongue muscles with opposing actions of tongue retraction and tongue protrusion, respectively. Experiments were performed using N=10 neonatal rat pups aged post-natal day 0-5 ( n=5 each of SL and GG). Motoneurons were back-labeled by injection of dextran rhodamine conjugated to Texas Red into either the SL or GG muscle. > 24-hours after injection, animals were anesthetized on ice and decapitated. The brainstem and spinal cord were removed and 250 μm transverse slices of the medulla containing the hypoglossal nucleus were obtained. SL or GG motor neurons were visualized under a fluorescence microscope and resting membrane potential, rheobase current, frequency-current relation and potassium currents were recorded using whole-cell patch clamp. Statistical analysis revealed that SL motoneurons were ~11 mV more depolarized than GG motoneurons (resting membrane potential of -49 vs -60 mV, p<0.05). Rheobase current (the minimal electrical current required to evoke an action potential) was greater in GG motoneurons than SL motoneurons (approximately 300 vs 150 pA, p<0.05). SL motoneurons had a higher firing rate than GG motoneurons in response to current injection ( p<0.05). Evaluation of neuronal potassium channel conductance showed that the magnitude of transient ( p < 0.01) and sustained (p < 0.01) potassium currents were greater in GG than SL motoneurons, consistent with our finding that resting membrane potential was more negative, and firing rate was slower, in GG than SL motoneurons. Finally, additional SL motoneuron recordings were performed to evaluate for potential sex differences in N=12 (6 male) rat pups aged post-natal day 0-5. Preliminary analysis revealed no significant difference in resting membrane potential between male (-49 mV) and female (-52 mV) SL motoneurons, suggesting that the properties of a specific hypoglossal motoneuron pool are consistent across sexes. Overall, these results demonstrate that GG motoneurons are less excitable than SL motoneurons, which supports the idea that intrinsic and extrinsic tongue muscles are driven by physiologically distinct motoneuron pools. This work has potential to guide development of therapeutics for disordered speech, breathing, and swallowing, all of which depend on proper neuromotor control of the tongue. This work was funded by NIH 5R01DC020889-02. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effect of Wi-Fi exposure and edible bird nest supplementation on the testicular oxidative stress status and sperm quality in male Sprague-Dawley rat pups

Effect of Wi-Fi exposure and edible bird nest supplementation on the testicular oxidative stress status and sperm quality in male Sprague-Dawley rat pups

Alleviating Neonatal Intensive Care Unit Stress: A Chinese Medicine Approach in Neonatal Rats.

Premature infants are exposed to numerous stressors in neonatal intensive care unit (NICU) during a crucial period for brain development; this period exerts long-term influences on cognitive and behavioral development. To evaluate the effect of NICU-related stress on neonatal rat pups and explore the effect of Chinese medicine treatment (CMT). Sixty male rat pups were randomly assigned to three groups: the control group, the NICU group (NICU-related stress), and the CMT group (NICU-related stress plus CMT). All stressors and interventions were administered from 0 to 7 days after birth. Body weight, serum corticosterone levels, and behavior in the open field (OF) test, elevated plus maze (EPM) test, sucrose preference test, and Morris water maze (MWM) test were recorded, and blood samples were collected at five different time points (T0, T1, T2, T3, and T4). The body weights of rats in the CMT and control groups were heavier than those in the NICU group in both early life and adulthood (P < 0.05). Serum corticosterone levels significantly differed with time (except T0 vs. T1 and T3 vs. T4) but did not significantly differ among the three groups (F = 0.441, P = 0.894). Regardless of age, spatial memory and anxiety-like and depression-like behavior did not differ among the three groups. NICU-related stress exerted a long-term effect on rat growth and development but did not affect spatial memory, anxiety-like behavior, depression-like behavior, or serum corticosterone levels. CMT alleviated the impact of NICU-related stress on rats and promoted the growth and development of neonatal rats.

Type 2 diabetes mellitus facilitates status epilepticus in adult rats: Seizure severity, neurodegeneration, and oxidative stress.

The goal of this research was to evaluate the effect of DM type 2 (DM2) on SE severity, neurodegeneration, and brain oxidative stress (OS) secondary to seizures. DM2 was induced in postnatal day (P) 3 male rat pups by injecting streptozocin (STZ) 100 mg/kg; control rats were injected with citrate buffer as vehicle. At P90, SE was induced by the lithium-pilocarpine administration and seizure latency, frequency, and severity were evaluated. Neurodegeneration was assessed 24 h after SE by Fluoro-Jade B (F-JB) staining, whereas OS was estimated by measuring lipid peroxidation and reactive oxygen species (ROS). DM2 rats showed an increase in latency to the first generalized seizure and SE onset, had a higher number and a longer duration of seizures, and displayed a larger neurodegeneration in the hippocampus (CA3, CA1, dentate gyrus, and hilus), the piriform cortex, the dorsomedial nucleus of the thalamus and the cortical amygdala. Our results also show that only SE, neither DM2 nor the combination of DM2 with SE, caused the increase in ROS and brain lipid peroxidation. DM2 causes higher seizure severity and neurodegeneration but did not exacerbate SE-induced OS under these conditions. Our research performed in animal models suggests that type 2 diabetes mellitus (DM2) may be a risk factor for causing higher seizure severity and seizure-induced neuron cell death. However, even when long-term seizures promote an imbalance between brain pro-oxidants and antioxidants, DM2 does not exacerbate that disproportion.

Perinatal hypoxia weakens anticontractile influence of NO in rat arteries during early postnatal period.

Perinatal hypoxia affects a lot of neonates worldwide every year, however its effects on the functioning of systemic circulation are not clear yet. We aimed at investigation the effects of perinatal hypoxia on the second day of life on the functioning of the rat systemic vasculature in early postnatal period. 2-day-old male rat pups were exposed to normobaric hypoxia (8% O2, 92% N2) for 2 hours. At the 11-14 days cutaneous (saphenous) arteries were isolated and studied by wire myography and Western blotting. Hypoxia weakened the contribution of anticontractile influence of NO, but did not affect the contribution of Rho-kinase or Kv7 channels to the contraction to α1-adrenergic agonist methoxamine. The content of eNOS and protein kinase G were not altered by hypoxic conditions. Perinatal hypoxia in rats at the second day of life leads to the decrease of anticontractile effect of NO in the systemic arteries in early postnatal ontogenesis (at the age of 11-14 days). Decreased anticontractile effect of NO can be the reason for insufficient blood supply and represent a risk factor for the development of cardiovascular disorders. The mechanisms of perinatal hypoxia influences on systemic circulation are almost unknown. We have shown that perinatal hypoxia weakens anticontractile influence of nitric oxide in early postnatal period. The influence of perinatal hypoxia on systemic circulation should be taken into account during treatment of newborns suffered from the lack of oxygen.

Impact of altered environment and early postnatal methamphetamine exposure on serotonin levels in the rat hippocampus during adolescence

BackgroundMethamphetamine (MA) is a highly abused psychostimulant across all age groups including pregnant women. Because developing brain is vulnerable by the action of drugs, or other noxious stimuli, the aim of our study was to examine the effect of early postnatal administration of MA alone or in combination with enriched environment (EE) and/or stress of separate housing, on the levels of serotonin (5HT) in the hippocampus of male rat pups at three stages of adolescence (postnatal day (PND) 28, 35 and 45). MA (5 mg/kg/ml) was administered subcutaneously (sc) to pups (direct administration), or via mothers' milk between PND1 and PND12 (indirect administration). Controls were exposed saline (SA). Pups were exposed to EE and/or to separation from the weaning till the end of the experiment.ResultsOn PND 28, in sc-treated series, EE significantly increased the muted 5HT in SA pups after separation and restored the pronounced inhibition of 5HT by MA. No beneficial effect of EE was present in pups exposed to combination of MA and separation. 5HT development declined over time; EE, MA and separation had different effects on 5HT relative to adolescence stage.ConclusionsPresent study shows that MA along with environment or housing affect 5HT levels, depending on both the age and the method of application (direct or indirect). These findings extend the knowledge on the effects of MA alone and in combination with different housing conditions on the developing brain and highlight the increased sensitivity to MA during the first few months after birth.

Neonatal di-(2-ethylhexyl)phthalate exposure induces permanent alterations in secretory CRH neuron characteristics in the hypothalamus paraventricular region of adult male rats

Corticotrophin-releasing hormone (CRH) neurons in the hypothalamic paraventricular nucleus (PVN) play a critical role in the modulation of the hypothalamic–pituitary–adrenal (HPA) axis. Early-life exposure to di-(2-ethylhexyl) phthalate (DEHP) has been associated with an increased risk of developing psychiatric disorders in adulthood. The present work was designed to explore the impact of neonatal exposure to DEHP on adult PVN CRH neuronal activity. DEHP or vehicle was given to male rat pups from PND16 to PND22. Then, anxiety-like behaviors, serum corticosterone and testosterone, immunohistochemistry, western blotting, fluorescence in situ hybridization and acute ex vivo slice electrophysiological recordings were used to evaluate the influence of DEHP on adult PVN secretory CRH neurons. Neonatal DEHP-exposed rats exhibited enhanced anxiety-like behaviors in adults, with an increase in CORT. Secretory CRH neurons showed higher spontaneous firing activity but could be inhibited by GABAAR blockers. CRH neurons displayed fewer firing spikes, prolonged first-spike latency, depolarizing shifts in GABA reversal potential and strengthened GABAergic inputs, as indicated by increases in the frequency and amplitude of sIPSCs. Enhancement of GABAergic transmission was accompanied by upregulated expression of GAD67 and downregulated expression of GABABR1, KCC2 and GAT1. These findings suggest that neonatal exposure to DEHP permanently altered the characteristics of secretory CRH neurons in the PVN, which may contribute to the development of psychiatric disorders later in life.

In silico and in vivo analysis of the relationship between ADHD and social isolation in pups rat model: Implication of redox mechanisms, and the neuroprotective impact of Punicalagin

Attention deficit hyperactivity disorder (ADHD) has high incidence rate among children which may be due to excessive monosodium glutamate (MSG) consumption and social isolation (SI). AimWe aimed to explore the relationships between MSG, SI, and ADHD development and to evaluate the neuroprotective potential of Punicalagin (PUN). MethodsEighty male rat pups randomly distributed into eight groups. Group I is the control, and Group II is socially engaged rats treated with PUN. Groups III to VII were exposed to ADHD-inducing factors: Group III to SI, Group IV to MSG, and Group V to both SI and MSG. Furthermore, Groups VI to VIII were the same Groups III to V but additionally received PUN treatment. Key findingsExposure to MSG and/or SI led to pronounced behavioral anomalies, histological changes and indicative of ADHD-like symptoms in rat pups which is accompanied by inhibition of the nuclear factor erythroid 2-related factor 2 (Nrf2)/Heme-oxygenase 1 (HO-1)/Glutathione (GSH) pathway, decline of the brain-derived neurotrophic factor (BDNF) expression and activation of the Toll-like receptor 4 (TLR4)/Nuclear factor kappa B (NF-kB)/NLR Family Pyrin Domain Containing 3 (NLRP3) pathway. This resulted in elevated inflammatory biomarker levels, neuronal apoptosis, and disrupted neurotransmitter equilibrium. Meanwhile, pretreatment with PUN protected against all the previous alterations. SignificanceWe established compelling associations between MSG consumption, SI, and ADHD progression. Moreover, we proved that PUN is a promising neuroprotective agent against all risk factors of ADHD.

The role of thymus graft on the onset of puberty in juvenile male rats

There exists a bidirectional relation between the thymus gland and the hypothalamo- hypophysial-gonadal axis. The thymus secretes various hormones, some of which can regulate the reproductive axis. So, it is worth to explore the possible role of an additional thymus on the onset of puberty in male albino rats. Two groups of male rats aged 5 and 10 days were used for the study. Each subgroup consisted of 4 pups each in control and experimental group. Thymus glands for graft were obtained from newborn male rat pups. Depending on the age group, 5 day or 10-day-old male rat pup were anaesthetized, 2-3 mm incision was made, and a thymus gland was grafted to the axilla. Sham operations were performed to the control pups. Without handling, animals were observed daily for the onset of puberty. On the day of descent of testes, body weight of the animal was noted, blood was collected and used for radio immunoassay. All morphometric measurements were done using an occular micrometer. Volume fraction of seminiferous tubules, intertubular connective tissue of testes, cortex and medulla of the thymus were estimated by point count method. In both the age groups thymus graft advanced the age of descent of testes, and increased body weight and organ weight. It also increased the serum hormone levels. In conclusion, this study indicates that an additional thymus gland has a positive effect on the male reproductive system towards pro-gonadal action, and this effect is more pronounced in older-age groups of rats.

Effects of Nicotine Administration in an Enriched Environment on the Behavior of Male MK-801-Exposed Rats.

Smoking is more common in patients with schizophrenia than in healthy populations. Some controversial hypotheses connect the disease with the high prevalence of smoking. Moreover, environmental factors affect the severity of the positive and negative symptoms of schizophrenia. The current study aimed to assess the effect of enriched environment (EE) and nicotine on the MK-801 animal model of schizophrenia. Male Wistar rat pups randomly received saline or MK-801 (dose:1 mg/kg) for five days from the sixth postnatal day (P) until the tenth. The pups were placed in EE or standard cages (SCs) after weaning (P21). Morris water maze (MWM) was used to assess spatial learning and memory. The rats received 0.6 mg/kg nicotine twice for three days at the end of the second month and were examined in an open-field box and three-chamber social interaction test. MK-801 rats' behaviors were the same as those of the saline rats when they were exposed to nicotine. No positive effects of EE were observed when the animals were exposed to nicotine. The results suggested that nicotine decreased schizophrenia-like symptoms and covered the positive effects of EE.

Early-life ozone exposure modulates region-specific gene expression in the developing rat lung

Early-life ozone exposure disrupts normal patterns of lung development, but the molecular determinants underlying these changes are not well understood. This study aimed to elucidate changes in gene expression following episodic ozone exposure to identify potential mechanisms of ozone-mediated impairments in lung development. Rat pups were exposed to either filtered air or ozone (0.5 ppm, 6 hr./day, 5 days/week) from postnatal day (PND) 7–28 (16 dams total with 8 pups each, 4 M & 4 F) and sacrificed at either PND 30–31 or PND 80–84. Lung microdissection isolated major regions for RNA-Seq analysis. Ozone modified inherent differences in gene expression between lung regions in both male and female rat pups, whereas statistically significant changes in gene expression directly attributed to ozone were only identified in females. The greatest number of differentially expressed genes was observed between the distal airways and the parenchyma of ozone-exposed juvenile female rats, with 355 genes being differentially expressed. Genes modulating epithelial-to-mesenchymal transition, cell growth, and adhesion were differentially expressed in the parenchyma of ozone exposed juvenile females, suggesting that episodic ozone exposure may affect branching morphogenesis and lung cell growth. Importantly, our study provides novel targets for future experiments investigating the impact of ozone on lung development.

Identification of Metabolomic Signatures for Ischemic Hypoxic Encephalopathy Using a Neonatal Rat Model.

A study was performed to determine early metabolomic markers of ischemic hypoxic encephalopathy (HIE) using a Rice-Vannucci model for newborn rats. Dried blood spots from 7-day-old male and female rat pups, including 10 HIE-affected animals and 16 control animals, were analyzed by liquid chromatography coupled with mass spectrometry (HPLC-MS) in positive and negative ion recording modes. Multivariate statistical analysis revealed two distinct clusters of metabolites in both HPLC-MS modes. Subsequent univariate statistical analysis identified 120 positive and 54 negative molecular ions that exhibited statistically significant change in concentration, with more than a 1.5-fold difference after HIE. In the HIE group, the concentrations of steroid hormones, saturated mono- and triglycerides, and phosphatidylcholines (PCs) were significantly decreased in positive mode. On the contrary, the concentration of unsaturated PCs was increased in the HIE group. Among negatively charged molecular ions, the greatest variations were found in the categories of phosphatidylcholines, phosphatidylinositols, and triglycerides. The major metabolic pathways associated with changed metabolites were analyzed for both modes. Metabolic pathways such as steroid biosynthesis and metabolism fatty acids were most affected. These results underscored the central role of glycerophospholipid metabolism in triggering systemic responses in HIE. Therefore, lipid biomarkers' evaluation by targeted HPLC-MS research could be a promising approach for the early diagnosis of HIE.