Lead-exposed Rats Research Articles

Effectiveness of Resveratrol Supplement on Some Biochemical Criteria and Bone in Lead-Exposed Rats

Effectiveness of Resveratrol Supplement on Some Biochemical Criteria and Bone in Lead-Exposed Rats

Zinc improves sexual performance and erectile function by preventing penile oxidative injury and upregulating circulating testosterone in lead-exposed rats

ABSTRACTAim:The present study evaluated the effect of lead exposure with and without zinc therapy on male sexual and erectile function.Methods:Twenty male Wistar rats were randomly assigned into four groups; the control, zinc-treated, lead-exposed, lead + zinc-treated groups. Administrations were per os daily for 28 days.Results:Zinc co-administration significantly improved absolute and relative penile weights and the latencies and frequencies of mount, intromission, and ejaculation in lead-exposed rats. Also, zinc ameliorated lead-induced reductions in motivation to mate and penile reflex/erection. These findings were accompanied by attenuation of lead-induced suppression of circulating nitric oxide (NO), penile cyclic guanosine monophosphate (cGMP), dopamine, serum luteinizing hormone, follicle-stimulating hormone, and testosterone. In addition, zinc alleviated lead-induced upregulation of penile activities of acetylcholinesterase and xanthine oxidase (XO), and uric acid (UA) and malondialdehyde (MDA) levels. Furthermore, zinc ameliorated the lead-induced decline in penile nuclear factor erythroid 2-related factor 2 (Nrf2) and reduced glutathione (GSH) levels, and catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) activities.Conclusion:This study revealed that co-administration of zinc improves lead-induced sexual and erectile dysfunction by suppressing XO/UA-driven oxidative stress and upregulating testosterone via Nrf2-mediated signaling.

Effect of Berberine on the Status of Antioxidants in the Heart of Lead-Exposed Rats

Effect of Berberine on the Status of Antioxidants in the Heart of Lead-Exposed Rats

The Effect of Lactobacillus fermentum Against Lead-induced Oxidative Damages in Rat Kidneys

Background: Kidneys are the most vulnerable organs with respect to oxidative stress caused by lead poisoning. In this study, renal biomarkers were investigated in rats, exposed to lead after treatment with or without Lactobacillus fermentum. Methods: Twenty-four rats were divided into four groups of five each as follows: a) control, b) lead-exposed, c) Lactobacillus fermentum–treated, and d) rats exposed to lead followed by treatment with L. fermentum. After eight weeks of treatment, the renal biomarkers in blood and antioxidant factors in the kidneys were evaluated. The kidneys were also examined histopathologically for alterations due to lead exposure. Results: In lead-exposed rats, the creatinine, urea, uric acid, malondialdehyde, and tissue lead contents were significantly higher, while catalase, glutathione peroxidase and glutathione levels were lower than those found in the controls. After treatment of lead-exposed rats with L. fermentum, the levels of these factors were significantly lower and the last two factors were higher compared to those of the lead-exposed group. There was no significant change in the level of catalase. The histopathological changes due to lead exposure in these rats decreased after treatment with L. fermentum. Conclusion: The results indicated that L. fermentum reduced the toxic effects of lead on the kidneys, either by potentiating the renal antioxidant system or by removing lead from the treated rats, or both. Further studies are warranted to elucidate the mechanisms by which L. fermentum exerts its anti-lead poisoning effects.

Sodium para-aminosalicylic acid ameliorates brain neuroinflammation and behavioral deficits in juvenile lead-exposed rats by modulating MAPK signaling pathway and alpha-synuclein

Lead (Pb) is a developmental neurotoxin that can disrupt brain development and damage the brain regions responsible for executive function, behavioral regulation and fine motor control. Sodium para-aminosalicylic acid (PAS-Na) is a non-steroidal anti-inflammatory drug that can cross the blood-brain barrier. The purpose of this study was to examine the effects of juvenile rat Pb exposure on behavioral changes and brain inflammation, and the efficacy of PAS-Na in ameliorating these effects. The results showed that Pb exposure during the juvenile period (from weaning to adult period) delayed rats’ growth development and impaired their motor learning. Pb exposure not only increased Pb concentrations in several brain regions (including hippocampus, striatum and substantia nigra), but also disrupted metal-homeostasis in the brain, as higher levels of iron (Fe) and calcium (Ca) were observed in the substantia nigra. Moreover, Pb activated the MAPK pathway and increased levels of inflammatory factors such as IL-1β, TNF-α and IL-6 in the hippocampus, striatum and substantia nigra. Furthermore, Pb increased the levels of alpha-synuclein (α-syn) in these brain sites. PAS-Na improved the motor deficits and brain inflammation in the Pb-exposed rats. Moreover, the elevated Pb, Fe and Ca concentrations in the brain were significantly reduced by PAS-Na, which contains amino, carboxyl and hydroxyl functional groups, suggesting that it may act as a chelator of brain metals. In addition, PAS-Na inhibited the Pb-induced MAPK pathway activation and α-syn accumulation in the same brain regions. Taken together, our novel study suggest that PAS-Na shows efficacy in improving the Pb-induced behavioral changes in rats by inhibiting MAPK-dependent inflammatory pathways and reducing α-syn accumulation.

Effects of folic acid on oxidative damage of kidney in lead-exposed rats.

Lead (Pb) has many applications in daily life, but in recent years, various problems caused by lead exposure have aroused people's concern. Folic acid is widely found in fruits and has received more attention for its antioxidant function. However, the role of folic acid in lead-induced kidney injury in rats is unclear. This study was designed to investigate the effects of folic acid on oxidative stress and endoplasmic reticulum stress in the kidney of rats caused by lead exposure. Forty specific pathogen-free male Rattus norvegicus rats were randomly divided into control, lead, intervention, and folic acid groups. The levels of SOD, GSH-Px, GSH, and MDA were measured by biochemical kits. The protein levels of Nrf2, HO-1, CHOP, and GRP78 were measured by immunofluorescence. This study showed that lead exposure increased the blood levels of lead in mice. However, the intervention of folic acid decreased the levels of lead, but the difference was not statistically significant. Lead exposure causes oxidative stress by decreasing kidney SOD, GSH-Px, and GSH levels and increasing MDA levels. However, folic acid alleviated the oxidative damage caused by lead exposure by increasing the levels of GSH-Px and GSH and decreasing the levels of MDA. Immunofluorescence results showed that folic acid intervention downregulated the upregulation of kidney Nrf2, HO-1, GRP78, and CHOP expression caused by lead exposure. Overall, folic acid alleviates kidney oxidative stress induced by lead exposure by regulating Nrf2 and HO-1, while regulating CHOP and GRP78 to mitigate apoptosis caused by excessive endoplasmic reticulum stress.

The role of probiotic intervention in regulating gut microbiota, short-chain fatty acids and depression-like behavior in lead-exposed rats.

The aim of this study was to observe the depression-like behavior changes of rats exposed to lead with or without probiotic intervention, and to investigate changes in the gut microbiota and fecal short-chain fatty acids (SCFAs) levels after lead exposure, and the possible functions of probiotics in this process. Adult male Sprague Dawley rats were exposed to a 300 mg/l lead acetate solution for 24 weeks, with or without probiotic (freeze-dried powder containing Lactobacillus and Bifidobacterium: 6 billion live bacteria/2 g) intervention in weeks 17-24. The sucrose preference test (SPT), the forced swim test (FST), and the tail suspension test (TST) were preformed to study the depression- like behaviors of these rats. The alteration of rat gut microbiota induced by lead exposure was analyzed by 16S rRNA sequencing, and the levels of fecal SCFAs were detected using gas chromatography. Neurobehavioral tests showed that lead exposure induced depression-like behavior in rats, including reduced sucrose preference in the SPT, and increased immobility times in the FST and the TST. Sequencing and gas chromatography showed that lead exposure changed the structure and the phylogenetic diversity of the gut microbiota, as well as significantly altered the levels of SCFAs. Moreover, the depression-like behaviors, and the changes in both gut microbiota and SCFAs, could be mitigated by probiotic intervention. Lead exposure not only changes the structure and diversity of the gut microbiome but also affects metabolic function. Probiotic intervention may be a novel initiative for the prevention and treatment of neurological damage following lead exposure. Int J Occup Med Environ Health. 2022;35(1):95-106.

Chronic Lead Exposure Alters Mineral Properties in Alveolar Bone

The objective of the present study was to investigate the effects of chronic lead exposure on the mineral properties of alveolar bone. For this purpose, female Wistar rats (n = 8) were exposed to 1000 ppm lead acetate in drinking water for 90 days, while the control group (n = 5) was treated with sodium acetate. The alveolar bone structure and chemical composition of the dissected mandibles were examined using micro-computed tomography (micro-CT), scanning electron microscopy (SEM), inductively coupled plasma optical emission spectrometry (ICP-OES), attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), and X-ray diffraction (XRD) techniques to determine possible alterations in alveolar bone due to lead exposure. In addition, changes in bone mechanical properties were analysed using a three-point bending test. Exposure to lead induced notable changes in bone mineralization and properties, specifically a reduction of the trabecular thickness and bone mineral density. Furthermore, there was a reduction in carbonate content and an increase in bone mineral crystallinity. These changes in bone mineralization could be explained by an alteration in bone turnover due to lead exposure. Three-point bending showed a trend of decreased displacement at failure in the mandibles of lead-exposed rats, which could compromise the mechanical stability and normal development of the dentition.

Protective effects of folic acid on oxidative damage of rat spleen induced by lead acetate

Lead (Pb) is a heavy metal environmental pollutant that can cause functional damage and anemia of immune organs. More and more evidence indicate that the toxicity of lead was related to apoptosis driven by oxidative stress and endoplasmic reticulum stress. This article mainly discusses the protective effect and mechanism of folic acid intervention on lead-induced spleen injury and apoptosis. In this study, Sprague-Dawley rats were randomly divided into control group, lead exposure group (0.2% lead acetate), folic acid + lead group (0.4 mg/kg folic acid and 0.2% lead acetate), and folic acid group (0.4 mg/kg folic acid). By recording and calculating the rat's initial body weight, final body weight, net weight gain, daily weight gain, and spleen index, observe the rat's weight change and spleen weight. And adopt the immunofluorescence staining method to determine the expression level of NrF2, HO-1, GRP78, CHOP protein in the spleen. The results showed that The 0.4 mg/kg folic acid diet did not significantly improve in the body weight and spleen index of lead-exposed rats (P > 0.05). While compared with the control group, the expression levels of HO-1 and CHOP protein were significantly increased in the lead exposure group (P < 0.05), and the expression levels of HO-1 and CHOP protein were significantly reduced in the folic acid intervention group (P < 0.05). In conclusion, lead exposure increased the expression levels of HO-1 and CHOP in the spleen of rats, and caused damage to the spleen. Folic acid down-regulated the expression levels of HO-1 and CHOP proteins through the two pathways of NrF2/HO-1 and GRP78/CHOP, thereby exerting a certain protective effect and alleviating the spleen caused by lead-induced oxidative stress and endoplasmic reticulum stress damage.

D-serine reduces memory impairment and neuronal damage induced by chronic lead exposure.

Although exogenous D-serine has been applied as a neural regulatory intervention in many studies, the role played by D-serine in hippocampal injuries caused by lead exposure remains poorly understood. Rat models of chronic lead exposure were established through the administration of 0.05% lead acetate for 8 weeks. Simultaneously, rats were administered 30 or 60 mg/kg D-serine, intraperitoneally, twice a day. Our results showed that D-serine treatment shortened the escape latency from the Morris water maze, increased the number of times that mice crossed the original platform location, and alleviated the pathological damage experienced by hippocampal neurons in response to lead exposure. Although D-serine administration did not increase the expression levels of the N-methyl-D-aspartate receptor subtype 2B (NR2B) in the hippocampi of lead-exposed rats, 60 mg/kg D-serine treatment restored the expression levels of NR2A, which are reduced by lead exposure. These findings suggested that D-serine can alleviate learning and memory impairments induced by lead exposure and that the underlying mechanism is associated with the increased expression of NR2A in the hippocampus. This study was approved by the Animal Ethics Committee of North China University of Science and Technology, China (approval No. LX2018155) on December 21, 2018.

Nephroprotective Effects of Aqueous Extracts of Hibiscus sabdariffa Calyces and Jatropha curcas Leaves against Lead Toxicity

Background: Lead is a persistent heavy metal which has been found to be a multi-organ toxicant. In recent times, plants containing natural compounds with both chelating and antioxidant activities are considered as promising candidates for managing lead toxicity. Objectives: The present investigation was undertaken to evaluate the ameliorative potentials of aqueous extracts of Jatropha curcas (JC) leaves and Hibiscus sabdariffa (HS) calyces against renal toxicity resulting from lead acetate exposure. Materials and Methods: Ten groups of male Wistar rats were taken: The first and second groups represented the normal and lead acetate (PbA) (50mg/kg b.w) control groups respectively while groups 3 and 4 were given 100mg/kg JC and 200 mg/kg JC respectively. Groups 5 and 6 received 250 mg/kg HS and 500 mg/kg HS respectively. Groups 7-10 were given PbA (50mg/kg) and 100mg/kg JC, 200 mg/kg JC, 250mg/kg HS, 500mg/kg HS respectively. Rats were orally administered their relevant doses for 28 days. Blood samples were collected from heart puncture at the end of the experiment (28 days) for renal function analysis. Result: Serum creatinine and urea concentrations were significantly higher (p < 0.05) in the lead acetate group compared to the normal control. The renal morphology of the lead-exposed rats also revealed the degeneration and necrosis in tubules and swelling in the glomerulus. The significant increase in renal markers and morphological alterations after lead toxicity induction were moderately normalized by the administration of aqueous extracts of Jatropha curcas and Hibiscus sabdariffa. Conclusions: Results demonstrated moderate beneficial effects of J. curcas and H. sabdariffa treatment in managing Pb-induced tissue damage in the kidney.

CHANGES OF MYOCARDIUM CONTRACTILITY ASSOCIATED WITH A SUBCHRONIC LEAD INTOXICATION IN RATS

Introduction. There is a high chance of a link between cardiovascular conditions and occupational or environmental exposure to lead. Taking into account the peculiarities of lead intoxication and the metal common occurrence it appeared to necessarily prove further experimental research of lead cardiotoxicity. Material and methods. After repeated intraperitoneal administration of sublethal doses of lead acetate to outbred male rats 3 times a week for 5 weeks, there was obtained the moderately pronounced subchronic lead intoxication manifested by some characteristic features. Cardiotoxic effects on myocardial contractility were studied by the analysis of the mechanical activity of isolated preparations of right ventricular trabeculae and papillary muscles contracting in isotonic and physiological modes of loading. Myocardial contractile function was also studied at the molecular level by measuring the sliding velocity of reconstructed thin filaments over myosin. Results. In papillary muscles lead intoxication led to a decrease in the maximal rate of isotonic shortening for all afterloads and a decrease in the thin filament sliding velocity in the in vitro motility assay. The same type of muscle from lead-exposed rats displayed marked changes in most of the main characteristics of afterload contraction-relaxation cycles, but in trabeculae, these changes were less pronounced. The reported changes were attenuated to some extent in rats similarly exposed to lead while being treated with a Ca-containing bio protector. The amount of work produced by both muscle preparations was unchanged under lead intoxication over the entire range of afterloads, which is an evidence of adaptation to the production of adequate mechanical work despite resulting contractility disturbances. Conclusions. 1. Subchronic lead intoxication was shown to cause contractile dysfunction of rat myocardium. In papillary muscles the alterations were observed more than in trabeculae. The changes in contractile proteins corresponded with those seen in myocardium structures. 2. The reported changes were attenuated to some extent in rats being treated with a Ca-containing bio protector.

Microanatomy, lipid peroxidation and antioxidant system of the visual cortex of rats following withdrawal from prolonged lead nitrate administration

Exposure to lead (Pb) has been shown to alter the function of central nervous system and affect cholinergic neurons of the visual cortex in animal models. This study sought to investigate the withdrawal symptoms and oxidative stress on the visual cortex after lead exposure. A total of 20 healthy male Wistar rats were randomly divided into two groups (n=10): group A, control, received 10 ml/kg of distilled water for 30 days orally; group B, lead treated group, received 10 mg/kg of lead nitrate solution for 30 days orally. Group B was divided into two subgroups, group B1 serves as non-recovery while B2 serves as recovery (withdrawal). Five rats from each group were sacrificed under ether anesthesia 24 hours after the last oral administration of lead, while the remaining 5 rats (withdrawal subgroup) were sacrificed 30 days after the last oral administration of lead. The visual cortex was grossed from the brain tissue and processed for histology. Blood/serum samples were obtained and markers of oxidative stress (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPX]), and lipid peroxidation (malondialdehyde [MDA]) were analyzed. Lead-exposed rats display a significant reduction in the SOD, CAT, and GPX level as well as increased in MDA level. However, following a recovery period, a non-significant improvement was seen in the histoarchitecture of the visual cortex.

Long-term probiotic intervention mitigates memory dysfunction through a novel H3K27me3-based mechanism in lead-exposed rats

Chronic lead exposure is associated with the development of neurodegenerative diseases, characterized by the long-term memory decline. However, whether this pathogenesis could be prevented through adjusting gut microbiota is not yet understood. To address the issue, pregnant rats and their female offspring were treated with lead (125 ppm) or separately the extra probiotics (1010 organisms/rat/day) till adulthood. For results, memory dysfunction was alleviated by the treatment of multispecies probiotics. Meanwhile, the gut microbiota composition was partially normalized against lead-exposed rats, which in turn mediated the memory repairment via fecal transplantation trials. In the molecular aspect, the decreased H3K27me3 (trimethylation of histone H3 Lys 27) in the adult hippocampus was restored with probiotic intervention, an epigenetic event mediated by EZH2 (enhancer of zeste homolog 2) at early developmental stage. In a neural cellular model, EZH2 overexpression showed the similar rescue effect with probiotics, whereas its blockade led to the neural re-damages. Regarding the gut–brain inflammatory mediators, the disrupted IL-6 (interleukin 6) expression was resumed by probiotic treatment. Intraperitoneal injection of tocilizumab, an IL-6 receptor antagonist, upregulated the hippocampal EZH2 level and consequently alleviated the memory injuries. In conclusion, reshaping gut microbiota could mitigate memory dysfunction caused by chronic lead exposure, wherein the inflammation–hippocampal epigenetic pathway of IL-6-EZH2-H3K27me3, was first proposed to mediate the studied gut–brain communication. These findings provided insight with epigenetic mechanisms underlying a unique gut–brain interaction, shedding light on the safe and non-invasive treatment of neurodegenerative disorders with environmental etiology.

The protective effect of curcumin on the lipid peroxidation caused by lead poisoning in rat

Objective To evaluate the effect of curcumin on the lead burden in lead-exposed rats, and to study whether curcumin can influence the lipid peroxidation caused by lead exposure. Methods A total of 70 rats of 21-day-old rats were divided randomly to 7 groups, the control group was given normal diet and drinking water, the curcumin group was given curcumin only 1 month after normal drinking water being given; the other 5 lead-exposed groups were given 2 g/L of acetate lead in free drinking water for 1 month and then randomly divided into lead-exposed group, low, medium and high concentration curcumin groups and Dimercaptosuccinic acid(DMSA) group, relatively.Lead levels of lead-exposed rats were determined by using inductively coupled plasma mass spectrometry, and commercial kit was used to detect antioxidant enzymes, and glutathione related enzymes and lipid peroxides. Results The lead concentrations in the blood, hippocampus, liver and kidney of lead-exposed group increased, the levels of each group were (221.76±12.59) μg/L, (1.10±0.11) μg/g, (1.40±0.12) μg/g, (8.26±0.47) μg/g, and (57.58±6.09) μg/g, respectively; compared with the lead-exposed group, the lead concentrations reduced in the blood, hippocampus, liver and kidney significantly (F=90.67, 39.07, 27.34, 86.04, all P=0.000) in the curcumin-treated group, while the effect of curcumin in the bones showed no significant difference between groups(F=5.65, P=0.230). Lead could significantly improve the level of lipid peroxides in the serum and hippocampus, and curcumin-treated groups could significantly reduce the level of lipid peroxidation(F=58.03, 19.25, 32.27, 24.83, all P=0.000) and (F=28.18, 33.71, 38.95, 32.11, all P=0.000); lead could also reduce the antioxidant enzyme activity in the serum and hippocampus; curcumin-treated groups could significantly increase the antioxidant enzyme activity (F=18.24, 78.65, all P=0.000) and (F=13.68, 17.04, all P=0.000), respectively.The concentration in the curcumin group was better than that of DMSA group (P<0.05). Conclusions Curcumin can downregulate the lead concentrations in the blood, hippocampus, liver and kidney and improve the activity of antioxidant enzymes, inhibit the oxidative stress induced by lead, and thus resist the lead-induced damage. Key words: Lead; Curcumin; Neurologic damage; Reactive oxygen species

Protective Effects of Salidroside on Lead Acetate-induced Oxidative Stress and Hepatotoxicity in Sprague-Dawley Rats.

Lead has heavy metal toxicity which endangers human and animal health. Salidroside (SDS) is a natural antioxidant that has extensive pharmacological usage. However, its protective effects on lead-induced oxidative stress and hepatotoxicity has not been reported. In this study, we established an animal model to evaluate the protective effects of SDS on chronic lead exposure induced oxidative stress and hepatotoxicity. Forty healthy Sprague-Dawley (SD) rats were assigned to control group (control, animals were provided with distilled water, n = 10); lead acetate-exposed group (PbAc, animals received lead acetate solution of 500ppm for 60days, n = 10); low dosage of SDS-treated group (PbAc-SDS-L, lead acetate exposed animals were given intragastric SDS 150mg/kg body weight for 60days, n = 10); and high dosage of SDS-treated group (PbAc-SDS-H, lead acetate exposed animals were given intragastric SDS 300mg/kg body weight for 60days, n = 10). The results showed that lead exposure caused a significant increase in serum ALP, AST, ALT, and TB (P < 0.01), and these were reversed after treatment with salidroside for 60days. Compared to the control, the liver GSH, SOD, and GSH-Px were decreased significantly after lead acetate exposure (P < 0.01). However, after treatment with SDS for 60days, those were dose-dependently reversed. Similarly, MDA was significantly increased in the PbAc group (P < 0.01), and it was significantly decreased in SDS treatment group. Moreover, SDS ameliorated lead-induced congestion and necrosis of hepatocytes. In addition, the RT-PCR and immunohistochemistry results revealed that the PbAc group showed a significant increase in the protein and mRNA of cytochrome P450 2E1 (CYP2E1) and NADPH oxidase 2 (NOX2) in rat liver. Treatment with SDS significantly reversed CYP2E1 and NOX2 expressions in the liver of lead-exposed rats. The results above indicated that SDS has obvious antioxidant activity; it can cure liver injury caused by lead acetate by inhibiting oxidative stress and increasing the antioxidant stress activity, thus improving the liver tissue structure.

Further analysis of rat myocardium contractility changes associated with a subchronic lead intoxication

A moderate subchronic lead intoxication was observed in male rats after repeated intraperitoneal injections of lead acetate. Right ventricular trabeculae and papillary muscles were isolated for in vitro studying of the contraction-relaxation cycle under isotonic and physiological loading. The contractile function of the myocardium was also assessed by measuring the velocity of thin filament movement over myosin. Lead intoxication led in papillary muscles to a decrease in the maximal rate of isotonic shortening for all afterloads and a decrease in the thin filament sliding velocity. Papillary muscles from lead-exposed rats displayed marked changes in most of the main characteristics of afterload contraction-relaxation cycles, but in trabeculae these changes were less pronounced. The reported changes were attenuated to some extent in rats treated with a Ca-containing bioprotector. The amount of work produced by both types of heart muscle preparations was not changed by lead. Only in papillary muscles the load-dependent relaxation index was significantly increased in the lead-treated groups. Thus subchronic lead intoxication affects the peak rate of force development and relaxation properties of cardiac muscle contracting in isotonic/physiological regimes rather than the total amount of mechanical work, which may reflect adaptive changes in the myocardial function under decreased contractility.

Influence of clozapine on neurodevelopmental protein expression and behavioral patterns in animal model of psychiatric disorder induced by low-level of lead.

Exposure to lead during pregnancy is a risk factor for the development of psychiatric disorders in the offspring. In this study, we investigated whether exposure to low levels of lead acetate (0.2%) in drinking water during pregnancy and lactation causes behavioral impairment and affects the expression of proteins associated with neurodevelopment. Lead exposure altered several parameters in rat offspring compared with those unexposed in open-field, social interaction, and pre-pulse inhibition tests. These parameters were restored to normal levels after clozapine treatment. Western blot and immunohistochemical analyses of the hippocampus revealed that several neurodevelopmental proteins were downregulated in lead-exposed rats. The expression was normalized after clozapine treatment (5 mg/kg/day, postnatal day 35–56). These findings demonstrate that downregulation of several proteins in lead-exposed rats affected subsequent behavioral changes. Our results suggest that lead exposure in early life may induce psychiatric disorders and treatment with antipsychotics such as clozapine may reduce their incidence.

Transcriptome Study of Brain Nerve Impairment Induced by Pb Exposure

With the introduction of the global brain science program, the brain science and cognitive science are listed as one of the important research areas in China, the goal of which is to understand the function of the brain. In the human brain plan, the neurodegeneration and neurodevelopment in diseases and aging are one of the key areas of concern. However, lead is an environmental heavy metal neurotoxin, which can cause neurodegenerative diseases and affect brain health. At present, the mechanism of the lead-induced nervous system damage mainly focuses on the damage of lead to neurons, while the researches related to the repair of damaged nerve cells induced by the lead exposure have not been reported. The Transcriptome sequencing technology is direct detection of transcripts by the deep sequencing technology, which can more accurately measure the expression of transcripts, and is an inevitable link between genomic genetic information and the proteome of biological functions. In addition, the regulation of the transcription level is the most important regulation mode of organisms. Based on the characteristics of neurogenesis for nerve repair, the current study applied transcriptional sequencing technology to screen the differentially expressed genes in the choroid plexus of rats and to explore the changes in the expression of neurotrophic factors regulating neurogenesis in the choroid plexus of the lead-exposed rats. The results showed that the differentially expressed genes on choroid plexus of the lead exposed rats were related to neurogenesis. In the process of neurogenesis, the expression of nutritive and growth-promoting factors IGF1, EGFr, IGF1r, EGFr1, VEGF $\alpha $ , and TGF $\beta 2$ decreased, which suggested that these cytokines may be involved in the process of lead exposure neurogenesis, which needs further experimental verification. The findings of this study provide a new target for the mechanism research and prevention and control measures of brain nerve injury caused by the lead exposure.

Effects of ascorbic acid treatment on developmental alterations in calcium-binding proteins and gamma-aminobutyric acid transporter 1 in the cerebellum of lead-exposed rats during pregnancy and lactation.

In the present study, we investigated the effects of lead (Pb) and ascorbic acid co-administration on rat cerebellar development. Female rats were randomly divided into the following groups: control, Pb, and Pb plus ascorbic acid (PA) groups. From one week prior to mating, female rats were administered Pb (0.3% Pb acetate in drinking water) and ascorbic acid (100 mg/kg, oral intubation). The chemical administration was stopped on postnatal day 21 when the morphology of the offspring's cerebellum is similar to that of the adult brain. The blood Pb level was significantly increased following long-term Pb exposure. Ascorbic acid reduced Pb levels in the dams and offspring. Nissl staining demonstrated that the number of Purkinje cells was significantly reduced following Pb exposure, while ascorbic acid ameliorated this effect in the cerebellum of the offspring. Calcium-binding proteins, such as calbindin, calretinin, and parvalbumin were commonly expressed in Purkinje cells, and Pb exposure and ascorbic acid treatment resulted in similar patterns of change, namely Pb-induced impairment and ascorbic acid-mediated amelioration. The gamma-aminobutyric acid transporter 1 (GABAT1) is expressed in the pinceau structure where the somata of Purkinje cells are entwined in inhibitory synapses. The number of GABAT1-immunoreactive synapses was reduced following Pb exposure, and ascorbic acid co-treatment prevented this effect in the cerebellar cortex. Therefore, it can be concluded that ascorbic acid supplementation to mothers during gestation and lactation may have potential preventive effects against Pb-induced impairments in the developing cerebellum via protection of inhibitory neurons and synapses.