Sialic Acid Enhanced the Antistress Capability under Challenging Situations by Increasing Synaptic Transmission.

BACKGROUND: In early life, sialic acid (SA) plays a crucial role in neurodevelopment and neuronal function. However, it remains unclear whether and how SA supplementation in early life promotes behavioral response to stress in adolescence. OBJECTIVES: This study aimed to examine the effects and mechanisms of SA on the antistress capability under challenging situations. METHODS: In this study, C57BL/6 mice were daily supplemented with 1 µL SA solution/g body weight at the dose of 10 mg/kg/d from postnatal day (PND) 5-45. The antistress behaviors, including open field, elevated plus maze, forced swimming test, and tail suspension test, were performed at PND 46, PND 48, PND 50, and PND 52 to detect the antistress ability of SA, respectively. RESULTS: Our results showed that SA-treated mice were more active in facing challenging situations. The fiber photometry experiment showed that SA promoted the excitatory neuronal response in the medial prefrontal cortex (mPFC), which was extensively interconnected to stress. Besides, electrophysiological results revealed SA enhanced synaptic transmission rather than neuronal excitability of mPFC excitatory neurons. It was also supported by the increasing spine density of mPFC excitatory neurons. At the molecular amount, the SA elevated the transmitter release-related proteins of mPFC, including Synapsin 1 and vesicular glutamate transporter 1 (VGlut 1). Furthermore, SA supplementation enhanced synaptic transmission mainly by altering the kinetics of synaptic transmission. CONCLUSIONS: The SA supplementation enhanced the response capability to stress under challenging situations, and the enhanced synaptic transmission of mPFC excitatory neurons may be the neurological basis of active response under challenging situations. In general, our findings suggested that SA supplementation in early life can promote stress resistance in adolescence.

Diagnosis and treatment of pericallosal artery aneurysms.

OBJECTIVE: Pericallosal artery aneurysms are not common clinically. The microsurgery and endovascular therapy are surgically challenging operations. The objective of the study is to summarize their clinical symptoms and optimal treatment strategies of pericallosal artery aneurysms. METHODS: Nine cases of pericallosal artery aneurysms detected by digital subtraction angiography (DSA) were reviewed. The clinical manifestation, brain imaging characteristics, and optimal treatment methods were summarized. RESULTS: Patients with spontaneous aneurysm had good clinical outcomes after endovascular coiling or microsurgical clipping treatment. There were no any neurological function deficits in five patients. One patient suffered from permanent neurological function deficits. Patients with traumatic aneurysm pericallosal had relatively poor outcomes, including two patients showing disturbed consciousness and the paralysis of the lower limbs with slow recovery, and one patient was dead after the surgery. CONCLUSION: Spontaneous subarachnoid hemorrhage and interhemispheric fissure hematoma suggest spontaneously pericallosal aneurysm, while traumatic corpus callosum hematoma as well the accompanying embryo of intraventricular hemorrhage suggest traumatic pericallosal aneurysm. Endovascular embolization is the primary surgical treatment for pericallosal aneurysm, while patients with pericallosal aneurysm are not suitable for surgical treatment. Microsurgical clipping treatment may be a choice. However, both of these treatment strategies have high risk.

Epigallocatechin-3-gallate Inhibits LPS/AßO-induced Neuroinflammation in BV2 Cells through Regulating the ROS/TXNIP/NLRP3 Pathway.

Neuroinflammation is a key factor in cognitive dysfunction and neurodegenerative diseases such as Alzheimer's disease (AD), so inhibiting neuroinflammation is considered as a potential treatment for AD. Epigallocatechin-3-gallate (EGCG), a polyhydroxyphenol of green tea, has been found to exhibit anti-oxidative, anti-inflammatory and neuroprotective effects. The aim of this study was to investigate the inhibitory effect of EGCG on inflammation and its mechanism. In this study, BV2 cells were simultaneously exposed to lipopolysaccharides (LPS) and the amyloid-ß oligomer (AßO) to induce inflammatory microenvironments. Inflammatory cytokines and NLRP3 inflammasome-related molecules were detected by RT-PCR and Western Blot. The results show that EGCG inhibits LPS/AßO-induced inflammation in BV2 cells through regulating IL-1ß, IL-6, and TNF-α. Meanwhile, EGCG reduces the activation of the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome and levels of intracellular ROS in BV2 cells treated with LPS/AßO by affecting the mitochondrial membrane potential (MMP). Further research found that EGCG inhibited MMP through regulating thioredoxin-interacting protein (TXNIP) in LPS/AßO-induced neuroinflammation. In conclusion, EGCG may alleviate LPS/AßO-induced microglial neuroinflammation by suppressing the ROS/ TXNIP/ NLRP3 pathway. It may provide a potential mechanism underlying the anti-inflammatory properties of EGCG for alleviating AD.

Chronic Pb exposure impairs learning and memory abilities by inhibiting excitatory projection neuro-circuit of the hippocampus in mice.

Lead (Pb) is an environmental neurotoxic metal. Chronic Pb exposure causes behavioral changes in humans and rodents, such as dysfunctional learning and memory. Nevertheless, it is not clear whether Pb exposure disrupts the neural circuit. Thus, here we aim at investigating the effects the chronic Pb exposure on neural-behavioral and neural circuits in mice from prenatal to postnatal day (PND) 63. Pregnant mice and their male offspring were treated with Pb (150 ppm) until postnatal day 63. In this study, several behavior tests and Golgi-Cox staining methods were used to assess spatial memory ability and synaptogenesis. Virus-based tracing systems and immunohistochemistry assays were used to test the relevance of chronic Pb exposure with disrupted neural circuits. The behavioral experiments and Golgi-Cox staining results showed that Pb exposure impaired spatial memory and spine density in mice. The virus tracing results revealed that the Entorhinal cortex (EC) neurons could be directly projected to Cornuammonis 1 (CA1) and Dentate gyrus (DG), forming a critical circuit inhibited, in either a direct or indirect way, by Pb invasion. In addition, excitatory neural input from EC（labeled with CaMKII）to CA1 and DG was significantly attenuated by Pb exposure. In conclusion, our data indicated that Pb significantly impaired the excitatory connections from EC to the hippocampus (CA1 and DG), providing a novel neuro-circuitry basis for Pb neurotoxicity.

Establishment of a dexamethasone-induced zebrafish skeletal muscle atrophy model and exploration of its mechanisms.

BACKGROUND: Skeletal muscle atrophy is one of the main side effects of high-dose or continuous use of glucocorticoids (such as dexamethasone). However, there are limited studies on dexamethasone-induced skeletal muscle atrophy in zebrafish and even fewer explorations of the underlying molecular mechanisms. This study aimed to construct a model of dexamethasone-induced skeletal muscle atrophy in zebrafish and to investigate the molecular mechanisms. METHODS: Zebrafish soaked in 0.01 % dexamethasone solution for 10 days. Loli Track (Denmark) and Loligo Swimming Respirometer were used to observe the effect of dexamethasone on swimming ability. The effects of dexamethasone on zebrafish skeletal muscle were observed by Transmission electron microscopy, H&E, and wheat germ agglutinin techniques. Enriched genes and signaling pathways were analyzed using Transcriptome sequencing. Further, the levels of mitochondrial and endoplasmic reticulum-related proteins were examined to investigate possible mechanisms. RESULTS: 0.01 % dexamethasone reduced zebrafish skeletal muscle mass (p < 0.05), myofibre size and cross-sectional area (p < 0.001), and increased protein degradation (ubiquitination and autophagy) (p < 0.05). In addition, 0.01 % dexamethasone reduced the swimming ability of zebrafish, as evidenced by the reluctance to move, fewer movement trajectories, decreased total distance traveled (p < 0.001), average velocity of movement (p < 0.001), oxygen consumption (p < 0.001), critical swimming speed (p < 0.01) and increased exhaustive swimming time (p < 0.001). Further, 0.01 % dexamethasone-induced mitochondrial dysfunction (decreased mitochondrial biogenesis, disturbs kinetic homeostasis, increased autophagy) and endoplasmic reticulum stress. CONCLUSIONS: 0.01 % dexamethasone induces skeletal muscle atrophy and impairs the swimming ability of zebrafish through mitochondrial dysfunction and endoplasmic reticulum stress.

Profile of N6-methyladenosine of Pb-exposed neurons presents epitranscriptomic alterations in PI3K-AKT pathway-associated genes.

Lead (Pb) is a pervasive heavy metal with multi-organ toxicity. However, the molecular mechanisms of Pb-induced neurotoxicity are not fully understood. The dynamics of N6-methylademine (m6A) is an emerging regulatory mechanism for gene expression, which is closely related to nervous system diseases. To elucidate the association between m6A modification and Pb-mediated neurotoxicity, primary hippocampal neurons exposed to 5 µM Pb for 48 h were used as the paradigm neurotoxic model in this study. According to the results, Pb exposure reprogrammed the transcription spectrum. Simultaneously, Pb exposure remodeled the transcriptome-wide distribution of m6A while disrupting the overall level of m6A in cellular transcripts. United analysis of MeRIP-Seq and RNA-Seq was applied to further identify the core genes whose expression levels are regulated by m6A in the process of lead-induced nerve injury. GO and KEGG analysis unveiled that the modified transcripts were overrepresented by the PI3K-AKT pathway. Mechanically, we elucidated the regulatory role of the methyltransferase like3 (METTL3) in the process of lead-induced neurotoxicity and the downregulation of the PI3K-AKT pathway. In conclusion, our novel findings shed new light on the functional roles of m6A modification in the expressional alternations of downstream transcripts caused by lead, providing an innovative molecular basis to explain Pb neurotoxicity.

Combined exposure of lead and cadmium leads to the aggravated neurotoxicity through regulating the expression of histone deacetylase 2.

Lead (Pb) and cadmium (Cd) are common heavy metals in the environment, exerting detrimental effects on central nervous system. Although increasing evidence demonstrated the Pb and Cd-induced neurotoxicity, the exact epigenetic mechanisms induced by combined exposure (co-exposure) of Pb and Cd are still unclear. In this study, the neurotoxicity of individual exposure and co-exposure to Pb and Cd in vivo (150 ppm and 5 ppm respectively) and in vitro (10 µM and 0.1 µM respectively) was investigated. The results showed that neurite outgrowth was inhibited by either individual or combined exposure to Pb/Cd, whereas the co-exposure aggravated the inhibitory effect in PC12 cells. The results of Morris Water Maze (MWM), Y maze and Golgi-Cox staining showed that either Pb or Cd alone exposure damaged the ability of learning and memory and decreased the dendritic spine density in both the hippocampal CA1 and DG area of Sprague---Dawley (SD) rats, and that the co-exposure aggravated the damages. Subsequently, histone deacetylase (HDAC) 2 was significantly increased in both hippocampal tissues and PC12 cells co-exposed to Pb and Cd, and the treatment of trichostatin A (TSA) and HDAC2-knocking down construct (shHDAC2) could markedly prevent neurite outgrowth impairment in PC12 cells. In summary, HDAC2 plays essential regulatory roles in neurotoxicity induced by the co-exposure to Pb and Cd, providing a potential molecular target for neurological intervention.

Dietary intake of polyunsaturated fatty acids alleviates cognition deficits and depression-like behaviour via cannabinoid system in sleep deprivation rats.

Sleep deprivation (SD) is a common feature in modern society. Prolonged sleep deprivation causes cognition deficits and depression-like behavior in the model of animal experiments. Endocannabinoid system are key modulators of synaptic function, which were related to memory and mood. Although the underlying mechanism remains unknown, several studies indicated the benefits of polyunsaturated fatty acids (PUFAs, linolenic acid, 39.7 %; linoleic acid, 28 %; and oleic acid, 22 %) on brain function through the endocannabinoid system. The present study aimed to evaluate the influence of dietary PUFAs on cognition deficits induced by sleep deprivation in Sprague Dawley rats. The rats were sleep deprivation continuously for 7 days and fed with PUFAs at three different dosages (2, 4 and 8 µl/g body weight) at the meantime. The effect of PUFAs on cognition was investigated by object recognition test while depressive-like behavior were detected using sucrose preference test and forced swim test. The mechanism of PUFAs was elucidated by hippocampal synaptic transmission analyses. The resluts revealed that SD led to the disorder of cognition and mood which was improved by the supplement of PUFAs. SD significantly increased the mEPSC frequency, and decreased the protein level of cannabinoid type-1 receptors (CB1R). These changes were restored by supplement of PUFAs, which showed a similar level to the control group. Behaviour tests showed that the positive effects on repairing cognition and anxiety disorders were almost completely abolished when the CB1R receptor antagonist rimonabant was applied to the SD rats. These findings indicated that PUFAs are a factor regulating cognition deficits and depression induced by SD via cannabinoid type-1 receptors.

Pb exposure induces an imbalance of excitatory and inhibitory synaptic transmission in cultured rat hippocampal neurons.

An appropriate balance of excitatory and inhibitory synapse maintains the network stability of the central nervous system. Our recent work showed lead (Pb) exposure can inhibit synaptic transmission in cultured hippocampal neurons. However, it is not clear whether Pb exposure disrupt the balance of excitatory and inhibitory synaptic transmission. Here, primary cultured hippocampal neurons from Sprague-Dawley (SD) rats were exposed to Pb (0.2 µM, 1 µM, 5 µM, respectively) from Days in Vitro (DIV) 7 to DIV 12 for 5 days and the excitatory and inhibitory synaptic transmission was examined. Patch clamp recording results showed that distinct from exposures of 0.2 µM and 5 µM, 1 µM Pb exposure significantly increased the mIPSC frequency and decreased the mEPSC frequency, leading to a uniform inhibitory outcome. Further, the number of inhibitory presynaptic puncta was significantly increased after 1 µM Pb exposure, while the number of excitatory presynaptic terminals was decreased. In addition 1 µM Pb increased the glutamic acid decarboxylase (GAD65) expression and the surface GABAA receptor (GABAAR) clusters. This shift might potentiate the synthesis of GABA and enhance the surface distribution of postsynaptic GABAAR clusters in hippocampus neurons. Together, these data showed that Pb exposure disrupted the balance of excitatory and inhibitory synaptic transmission via abnormal GABAergic neurotransmission.

Case-control study of blood lead levels and attention deficit hyperactivity disorder in Chinese children.

BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) and lead exposure are high-prevalence conditions among children. OBJECTIVE: Our goal was to investigate the association between ADHD and blood lead levels (BLLs) in Chinese children, adjusting for known ADHD risk factors and potential confounding variables. METHODS: We conducted a pair-matching case-control study with 630 ADHD cases and 630 non-ADHD controls 4-12 years of age, matched on the same age, sex, and socioeconomic status. The case and control children were systematically evaluated via structured diagnostic interviews, including caregiver interviews, based on the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., revised criteria (DSM-IV-R). We evaluated the association between BLLs and ADHD using the Pearson chi-square test for categorical variables and the Student t-test for continuous data. We then performed conditional multiple variables logistic regression analyses with backward stepwise selection to predict risk factors for ADHD. RESULTS: There was a significant difference in BLLs between ADHD cases and controls. ADHD cases were more likely to have been exposed to lead during childhood than the non-ADHD control subjects, with adjustment for other known risk factors [children with BLLs >or= 10 microg/dL vs.

Opposite effects of alpha-lipoic acid on antioxidation and long-term potentiation in control and chronically lead-exposed rats.

Among the developmental changes identified in rats exposed to lead are impairments in long-term potentiation (LTP) in the hippocampus and changes in the levels of reactive oxygen species (ROS) in cells and some soft tissues. alpha-Lipoic acid (LA) has been reported to be highly effective in improving the thiol capacity of the cells and in reducing lead-induced oxidative stress. To explore the effects of LA on LTP in chronically lead-exposed rats and the relationship between ROS and LTP in both control and lead-exposed rats, we have compared LTP and oxidative stress parameters in groups of lead-exposed and control rats with or without LA treatment (10, 25, 50, and 100 mg/kg through intraperitoneal injection). The capacity of LA to decrease hippocampal lead levels in lead-exposed rats was examined. We found that LA had no effects in decreasing the level of lead in the hippocampus, but it did appear to have both antioxidant properties and a reparatory effect on LTP amplitude in rats developmentally exposed to lead for 2 weeks following birth. Interestingly, bell-shaped dose-response curves emerged. In the lower LA dosage groups (10, 25 mg/kg LA), there was an increasing LTP amplitude. The strongest protective effect in terms of the induction and amplitude of LTP in the lead-exposed group with at 25 mg/kg LA; when higher dosages were applied (50, 100 mg/kg LA), the LTP amplitude decreased as compared to the 25 mg/kg LA treatment group. The administration of LA to control animals resulted in a significant impairment of LTP amplitude, with the 100 mg/kg LA treatment having harmful effects on the oxidative parameters. These differential effects of LA on LTP in control and lead-exposed rats may be due to the different redox status of the control and lead-exposed rats.

Phytohormone Abscisic Acid Improves Spatial Memory and Synaptogenesis Involving NDR1/2 Kinase in Rats.

The abscisic acid (ABA) is a phytohormone involved in plant growth, development and environmental stress response. Recent study showed ABA can also be detected in other organisms, including mammals. And it has been reported that ABA can improve learning and memory in rats. In this study, we attempted to investigate the effects of ABA on the alternation of dendritic spine morphology of pyramidal neurons in developmental rats, which may underlie the learning and memory function. Behavior tests showed that ABA significantly improved spatial memory performance. Meanwhile, Golgi-Cox staining assay showed that ABA significantly increased the spine density and the percentage of mushroom-like spines in pyramidal neurons of hippocampus, indicating that ABA increased dendritic spine formation and maturation, which may contribute to the improvement of spatial memory. Furthermore, ABA administration increased the protein expression of NDR1/2 kinase, as well as mRNA levels of NDR2 and its substrate Rabin8. In addition, NDR1/2 shRNA prohibited the ABA-induced increases in the expression of NDR1/2 and spine density. Together, our study indicated that ABA could improve learning and memory in rats and the effect are possibly through the regulation of synaptogenesis, which is mediated via NDR1/2 kinase pathway.

The protective effect of polysaccharide extracted from Portulaca oleracea L. against Pb-induced learning and memory impairments in rats.

This paper studied the extraction of polysaccharide from Portulaca oleracea L. (POP) by hot water extraction and ethanol precipitation. Structural properties of the extracted polymers were determined. POP was composed of rhamnose, arabinose and galactose in ratios of 1: 2.34: 3.07 with a molecular weight of 1.55 × 107 Da. The neuroprotective effect of POP on Pb-induced neuronal toxicity was then evaluated in vitro and in vivo test. Treatment with POP markedly increased the survival of PC12 cells and repressed the generation of reactive oxygen species following Pb exposure. In Morris water maze analysis, Pb exposure led to an increase in escape latency and a decrease in platform crossing times of rats in the probe test, which could be attenuated by POP treatment. Additionally, the Pb-induced loss of dendritic spine was recovered after feeding rats with POP at 600 mg/kg/day. These results indicated that Pb-induced cognitive impairments could be inhibited by POP.

Immunomodulating effects of fractioned polysaccharides isolated from Yu-Ping-Feng-Powder in cyclophosphamide-treated mice.

Yu-Ping-Feng-Powder (YP), a traditional Chinese medicine prescription, is widely applied in China for the cure and prevention of diseases related to immunodeficiency. To test whether the fractioned polysaccharides (YPF-P) isolated from YP have immunomodulating activities, the effects of YPF-P on cyclophosphamide (Cy)-treated mice were studied in relation to phagocytosis of macrophage, splenocyte proliferation, and humoral, and cellular immunity parameters. It was found that YPF-P enhances phagocytic activity, augments ConA- or LPS-stimulated T cell proliferation, increases the quantitative haemolysis of SRBC (QHS) and delayed-type hypersensitivity reaction (DTH) to dinitrofluorobenzene. Hence, YPF-P restored the immuno-competence suppressed by Cy. YPF-P also augmented IL-2 and IFN-gamma production, but failed to increase IL-4 production, which indicates that there is high probability that it enhance Th1 function. These results suggested that YPF-P has immunomodulating effects and that the polysaccharides constitute one of the active components of YP.

ß-Asarone Rescues Pb-Induced Impairments of Spatial Memory and Synaptogenesis in Rats.

Chronic lead (Pb) exposure causes cognitive deficits. This study aimed to explore the neuroprotective effect and mechanism of ß-asarone, an active component from Chinese Herbs Acorus tatarinowii Schott, to alleviate impairments of spatial memory and synaptogenesis in Pb-exposed rats. Both Sprague-Dawley developmental rat pups and adult rats were used in the study. Developmental rat pups were exposed to Pb throughout the lactation period and ß-asarone (10, 40mg kg-1, respectively) was given intraperitoneally from postnatal day 14 to 21. Also, the adult rats were exposed to Pb from embryo stage to 11 weeks old and ß-asarone (2.5, 10, 40mg kg-1, respectively) was given from 9 to 11 weeks old. The level of ß-asarone in brain tissue was measured by High Performance Liquid Chromatography. The Morris water maze test and Golgi-Cox staining method were used to assess spatial memory ability and synaptogenesis. The protein expression of NR2B subunit of NMDA receptor, Activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) and Wnt family member 7A (Wnt7a) in hippocampus, as well as mRNA expression of Arc/Arg3.1 and Wnt7a, was also explored. We found that ß-asarone could pass through the blood brain barrier quickly. And ß-asarone effectively attenuated Pb-induced reduction of spine density in hippocampal CA1 and dentate gyrus areas in a dose-dependent manner both in developmental and adult rats, meanwhile the Pb-induced impairments of learning and memory were partially rescued. In addition, ß-asarone effectively up-regulated the protein expression of NR2B, Arc and Wnt7a, as well as the mRNA levels of Arc/Arg3.1 and Wnt7a, which had been suppressed by Pb exposure. The results suggest the neuroprotective properties of ß-asarone against Pb-induced memory impairments, and the effect is possibly through the regulation of synaptogenesis, which is mediated via Arc/Arg3.1 and Wnt pathway.

Early developmental bisphenol-A exposure sex-independently impairs spatial memory by remodeling hippocampal dendritic architecture and synaptic transmission in rats.

Bisphenol-A (BPA, 4, 4'-isopropylidene-2-diphenol), a synthetic xenoestrogen that widely used in the production of polycarbonate plastics, has been reported to impair hippocampal development and function. Our previous study has shown that BPA exposure impairs Sprague-Dawley (SD) male hippocampal dendritic spine outgrowth. In this study, the sex-effect of chronic BPA exposure on spatial memory in SD male and female rats and the related synaptic mechanism were further investigated. We found that chronic BPA exposure impaired spatial memory in both SD male and female rats, suggesting a dysfunction of hippocampus without gender-specific effect. Further investigation indicated that BPA exposure causes significant impairment of dendrite and spine structure, manifested as decreased dendritic complexity, dendritic spine density and percentage of mushroom shaped spines in hippocampal CA1 and dentate gyrus (DG) neurons. Furthermore, a significant reduction in Arc expression was detected upon BPA exposure. Strikingly, BPA exposure significantly increased the mIPSC amplitude without altering the mEPSC amplitude or frequency, accompanied by increased GABAARß2/3 on postsynaptic membrane in cultured CA1 neurons. In summary, our study indicated that Arc, together with the increased surface GABAARß2/3, contributed to BPA induced spatial memory deficits, providing a novel molecular basis for BPA achieved brain impairment.

Multiple epigenetic factors predict the attention deficit/hyperactivity disorder among the Chinese Han children.

Attention deficit/hyperactivity disorder (ADHD) is one of the most common psychiatric disorders of childhood. Despite its prevalence, the critical factors involved in its development remain to be identified. It was recently suggested that epigenetic mechanisms probably contribute to the etiology of ADHD. The present study was designed to examine the associations of epigenetic markers with ADHD among Chinese Han children, aiming to establish the prediction model for this syndrome from the epigenetic perspective. We conducted a pair-matching case-control study, and the ADHD children were systematically evaluated via structured diagnostic interviews, including caregiver interviews, based on the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, revised criteria (DSM-IV-R). The expression levels of risk genes DAT1, DRD4, DRD5, as well as their promoter methylation, were determined respectively, followed by the expression profiles of histone-modifying genes p300, MYST4, HDAC1, MeCP2. The multivariate logistic regressions were performed to establish ADHD prediction models. All of the seven genes tested were identified as risk factors for ADHD. The methylation of one critical CpG site located upstream of DRD4 was shown to affect its transcription, suggesting a role in ADHD's development. Aberrant DNA methylation and histone acetylation were indicated in ADHD patients. In addition, a prediction model was established using the combination of p300, MYST4 and HDAC1, with the accuracy of 0.9338. This is, to our knowledge, the first study to clearly demonstrate the associations between epigenetic markers and ADHD, shedding light on the preliminary diagnosis and etiological studies of this widespread disorder.

Reparatory effects of nicotine on NMDA receptor-mediated synaptic plasticity in the hippocampal CA1 region of chronically lead-exposed rats.

Activation of neuronal nicotinic acetylcholine receptors (nAChRs) modulates the induction of long-term potentiation (LTP): a possible cellular mechanism of learning. To investigate the effect of nicotine on synaptic plasticity in chronically lead-exposed rats, field excitatory postsynaptic potentials and paired-pulse facilitation (PPF) were recorded in the CA1 area of hippocampal slices from chronically lead-exposed 23-30-day-old rats. The results showed the following. (1) Nicotine (1 microm) facilitated the induction of LTP in CA1 by a weak tetanic stimulation (100 Hz, 20 pulses), which does not by itself produce LTP in lead-exposed rats. This effect was significantly suppressed by mecamylamine, a nicotinic antagonist, suggesting that the facilitation of LTP was through nAChRs. (2) The nicotine-facilitated LTP was blocked by dihydro-beta-erythroidine (DHbetaE), a non-alpha7 nAChR antagonist, whereas long-term depression (LTD) was produced by the combination of nicotine and methyllycaconitine, a alpha7-nAChR antagonist. This type of LTD was blocked by DHbetaE. This suggested that several nAChR subtypes were involved in the nicotine-facilitated synaptic plasticity. (3) Nicotine enhanced PPF in the hippocampal CA1 region, and the nicotine-facilitated LTP in lead-exposed rats was blocked by either d-(-)-2-amino-5-phosphonopentanoic acid, the N-methyl-d-aspartate (NMDA) receptor antagonist, or picrotoxin, an antagonist of gamma-aminobutyric acid(A) receptors. We suggest that nicotine-facilitated synaptic plasticity was due to the activation of NMDARs by disinhibition of pyramidal cells through presynaptic nAChRs. This may represent the cellular basis of nicotine-facilitated cognitive enhancement observed in chronically lead-exposed rats.

[Effects of post material on stress distribution in dentine].

OBJECTIVE: To investigate stress distribution of different material restored post-cores in dentine and provide a theoretical guidance for clinical use. METHODS: A three-dimensional finite element model of maxillary central incisor restored with post-core and PFM crown was constructed by SCT scan technology. Based on this model, stress distribution in dentine was analyzed before and after post-core restorations with 6 different materials, including cast Ni-Cr alloy, cast titanium alloy, cast gold alloy, glass fiber reinforced composite, polythene fiber reinforced composite, and common composite resin. RESULTS: When the tooth was restored with cast Ni-Cr alloy post and PFM crown, the maximum tensile stress and Von Mises stress in dentin at post apex increased 152% and 162% respectively, compared with a tooth restored only with PFM crown. If polythene fiber reinforced composite was used as post material, the stress distribution did not significantly change. When the other materials were used for the post, the stress distribution changed greatly. The elastic modulus of post-core materials affected the stress distribution pattern in dentine. CONCLUSION: The materials with elastic modulus similar to that of dentin, such as polythene fiber reinforced composite, may be suitable for post restoration.