Abstract：
:Low-to-moderate level developmental and adult lead exposure produces retinal dysfunction and/or degeneration in humans and experimental animals. Although high level in vivo or in vitro lead disrupts blood-brain-barrier tight junctions and increases its permeability, the blood-retinal-barrier (BRB) has not been examined. There were four overall goals. First, generate environmentally relevant dose-response models of short-term lead exposure in adult rats. Second, assess retinal histology and functional integrity of the BRB. Third, investigate the transmembrane proteins occludin and claudin-5 as targets mediating the increased BRB permeability. Fourth, examine the contribution of the PI3K-Akt signaling pathway as a mechanism underlying increased BRB permeability. Young adult rats were given water, 0.01% or 0.02% lead drinking solutions for six weeks. In control, 0.01% and 0.02% groups the six week mean blood [Pb] were 1, 12.5 and 19μg/dl, respectively. We employed histology, stereology, quantitative image analysis, immunoblots and densitometry, and pharmacology techniques. Major findings were that adult lead exposure produced dose-dependent 1) decreases in outer and inner nuclear layer thickness, 2) increases in BRB permeability, 3) decreases in occludin and claudin-5 expression, 4) increases in pAkt (Ser473), but not pAkt (Thr308), expression, and 5) wortmannin partially or completely blocked the increased BRB permeability and changes in protein expression. These results indicate that lead-induced increases in PI3K-Akt signaling partially underlie the increased BRB permeability and advance our knowledge about lead-induced retinotoxicity. Furthermore, they suggest that environmental and occupational lead exposures are risk factors for increased BRB permeability in diseases such as age-related macular degeneration, diabetes and stroke.
journal_name
Neurotoxicologyjournal_title
Neurotoxicologyauthors
Shen XF,Huang P,Fox DA,Lin Y,Zhao ZH,Wang W,Wang JY,Liu XQ,Chen JY,Luo WJdoi
10.1016/j.neuro.2016.09.013subject
Has Abstractpub_date
2016-12-01 00:00:00pages
145-152eissn
0161-813Xissn
1872-9711pii
S0161-813X(16)30193-0journal_volume
57pub_type
杂志文章相关文献
NEUROTOXICOLOGY文献大全abstract：:Rats were anesthetized with urethane, implanted with stimulating and recording electrodes in the perforant path and dentate gyrus, and exposed to different doses of lindane. Analysis of evoked field potential responses indicated that lindane exposure resulted in consistent, dose-dependent changes. Two separable effect...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：
更新日期：1987-01-01 00:00:00
abstract：:Prior studies demonstrate a critical role for mesolimbic dopamine systems, particularly nucleus accumbens, in the mediation of fixed interval (FI) schedule-controlled behavior and an enhancement of nucleus accumbens dopamine activity as a mechanism of chronic postweaning lead (Pb)-induced increases in Fl response rate...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：10.1016/s0161-813x(02)00059-1
更新日期：2002-09-01 00:00:00
abstract：:Previous work has demonstrated that continual exposure to 0.2% lead (Pb) beginning at birth diminishes depolarization-induced hippocampal glutamate (GLU) and GABA release in vivo. The present study sought to extend these findings by examining Pb-induced changes as a function of exposure period. Rats were continually e...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：
更新日期：1999-08-01 00:00:00
abstract：:It has been suggested that exposure to pesticides might be involved in the etiology of Parkinson's disease (PD). We conducted an updated systematic review of the epidemiologic literature over the past decade on the relationship between pesticide exposure and PD, using the MEDLINE database. Despite methodological diffe...
journal_title：Neurotoxicology
pub_type： 杂志文章,评审
doi：10.1016/j.neuro.2012.05.011
更新日期：2012-10-01 00:00:00
abstract：:On the basis of the evidence that extracellular Zn2+ influx induced with AMPA causes Parkinson's syndrome in rats that apomorphine-induced movement disorder emerges, here we used a low dose of AMPA, which does not increase intracellular Zn2+ level in the substantia nigra pars compacta (SNpc) of young adult rats, and t...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：10.1016/j.neuro.2020.12.014
更新日期：2021-01-02 00:00:00
abstract：:This study investigated the effect of the pre- and perinatal exposure to di-(2-ethylhexyl) phthalate (DEHP) on the neuroendocrine parameters that regulate reproduction in peripubertal male rats. DEHP at dose of 3 and 30mg/kg bw/day was administered orally to female rat since pregnancy onset until weaning. The male lit...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：10.1016/j.neuro.2010.06.006
更新日期：2010-12-01 00:00:00
abstract：:To evaluate the role of diet composition on nerve agent toxicity, rats were fed four distinct diets ad libitum for 28 d prior to challenge with 110 μg/kg (1.0 LD(50), sc) soman. The four diets used were a standard rodent diet, a choline-enriched diet, a glucose-enriched diet, and a ketogenic diet. Body weight was reco...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：10.1016/j.neuro.2011.03.001
更新日期：2011-06-01 00:00:00
abstract：:Central respiratory chemosensitivity has been ascribed to CO2-sensitive neurons located on the ventral brainstem surface. The effects of cholinergic mechanisms on CO2-sensitive neuronal activity recorded extracellularly at the brainstem respiratory chemosensitive area at the caudal ventral medullary surface (cVMS) wer...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：
更新日期：1993-01-01 00:00:00
abstract：:The spatial and temporal patterns of spontaneous synchronous Ca2+ oscillations (SCOs) regulate physiological pathways that influence neuronal development, excitability, and health. Hippocampal neuronal cultures (HN) and neuron/glia co-cultures (HNG) produced from neonatal mice were loaded with Fluo-4/AM and SCOs recor...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：10.1016/j.neuro.2016.10.015
更新日期：2017-01-01 00:00:00
abstract：:A device using four infra-red light photocells per cage which monitor simultaneously the motility of 120 individual rodents, was developed at our institute. The measuring interval can be chosen freely, the starting time may be set freely and the test may last several weeks. The motility of the offspring (day 35-39) of...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：
更新日期：1989-10-01 00:00:00
abstract：:Electron microscopy has been used to characterize the products of the reactions of aluminum with DNA under three different conditions, one of which, pH 5 and Al (III)/DNA(P) ratio of 0.4, has been previously shown to produce reversible interstrand crosslinking in double-stranded DNA molecules. Under this condition, al...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：
更新日期：1989-07-01 00:00:00
abstract：:Several organolead compounds have been shown to inhibit both the basal and dopamine-sensitive forms of adenylate cyclase obtained from rat caudate nucleus. The mode of action of the trisubstituted lead compounds is shown to depend upon the form of adenylate cyclase studied. The dopamine-sensitive form of adenylate cyc...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：10.1016/0191-8869(82)90087-3
更新日期：1982-07-01 00:00:00
abstract：:Malaria is an infectious disease that is caused by different species of Plasmodium. Several antimalarial drugs are used to counter the spread and infectivity of Plasmodium species. However, humans are also vulnerable to many of the antimalarial drugs, including the quinoline-based drugs. In particular, the antimalaria...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：10.1016/j.neuro.2020.01.006
更新日期：2020-03-01 00:00:00
abstract：:The PCBs are members of the halogenated hydrocarbon class of environmental chemicals that includes the dibenzofurans and dioxins. The PCBs were used over a period of 40 years for number of industrial purposes. Their appearance in the ecosystem and biological samples from wildlife, as well as documented cases of accide...
journal_title：Neurotoxicology
pub_type： 杂志文章,评审
doi：
更新日期：1997-01-01 00:00:00
abstract：:The time dependent tissue/organ distribution of Pb resulting from repeated intragastric exposure of the preweanling rat to Pb acetate was investigated. On the day of parturition, 12 dams were assigned randomly either to control (nonhandled) or Pb-treated groups and their litters were culled to 8 pups. On days 6, 9, 12...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：
更新日期：1984-10-01 00:00:00
abstract：:Throughout the world, alum (aluminum sulfate) is used in municipal water treatment plants to clarify water. Alum treatment usually removes aluminosilicate particles from drinking water but can substantially increase its soluble aluminum content (Zhang et al., 1994; Tran et al., 1993; Kopp, 1970). Soluble aluminum is t...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：
更新日期：1995-04-01 00:00:00
abstract：:There are no Food and Drug Administration approved pharmacotherapies for methamphetamine (METH) overdose, thus identifying novel drug targets to prevent this devastating adverse event is a public-health imperative. Previous research suggests that serotonin and sigma receptors may contribute to the adverse effects of M...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：10.1016/j.neuro.2019.05.011
更新日期：2019-09-01 00:00:00
abstract：OBJECTIVE:The purpose of this investigation was to develop and apply case definitions of peripheral neuropathy (PN) derived from a set of individual measures of peripheral nerve function obtained in two epidemiological studies. METHODS:In the first study, retired workers of an industrial plant who were either previous...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：
更新日期：2000-10-01 00:00:00
abstract：:The recently published crystal structure of monoamine oxidase (MAO) B was a major breakthrough for structural and functional understanding of flavin containing amine oxidases: it opens a new era of research and provides new opportunities to those interested in the biochemistry and pharmacology of those important drug ...
journal_title：Neurotoxicology
pub_type： 杂志文章,评审
doi：10.1016/S0161-813X(03)00088-3
更新日期：2004-01-01 00:00:00
abstract：:In a previous in vitro study, we demonstrated the protective effects of a new drug, 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride (KHG26377), against glutamate-induced excitotoxicity in cultured glial cells. In this study, we explored the possible mechanisms underlying the neuroprotective and anti-inflammat...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：10.1016/j.neuro.2013.07.001
更新日期：2013-09-01 00:00:00
abstract：:Chronic exposure to Mn results in the development of a neurological disorder known as manganism characterized by neurological deficits resembling that seen in Parkinsonism. Although dopaminergic neurons within the nigrostriatal pathway appear intact, Mn-induced irregularities in DA transmission have been observed incl...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：10.1016/j.neuro.2013.01.002
更新日期：2013-03-01 00:00:00
abstract：:Environmental chemicals have a potential impact on children's health as the developing brain is much more vulnerable to injury caused by different classes of chemicals than the adult brain. This vulnerability is partly due to the fact that very complex processes of cell development and maturation take place within a t...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：10.1016/j.neuro.2009.11.006
更新日期：2010-09-01 00:00:00
abstract：:Mitoxantrone is an antineoplastic agent considered a potential human teratogen because of its mechanism of action and is classified by the US Food and Drug Administration in pregnancy category risk D. In the literature there are only four cases of women exposed to the drug in late pregnancy. We report the first case o...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：10.1016/j.neuro.2006.10.002
更新日期：2007-05-01 00:00:00
abstract：:The N-oxide of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is the major metabolite found in vivo and excreted in urine after the parenteral administration of the neurotoxicant, MPTP. In mice (C57BL/6), stereotaxic injection of MPTP N-oxide (15 micrograms) into the neostriatum produced dopamine (DA) depletion s...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：
更新日期：1991-07-01 00:00:00
abstract：:Gene expression profiles in several brain regions of adult male rats were evaluated following a d-amphetamine (AMPH) exposure paradigm previously established to produce AMPH neurotoxicity. Escalating doses of AMPH (5-30 mg/kg) were given over the course of 16 h per day in an 18 degrees C environment for 2 days. This p...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：10.1016/j.neuro.2003.08.005
更新日期：2004-06-01 00:00:00
abstract：:Aluminum compounds (Al) increased the membrane potential (Em) and decreased the input resistance (Rin) of identified snail neurons. The neuronal excitability increased after Al withdrawal in the washing period. Cumulative Al applications caused dose-dependent modulation of Em and Rin in most of the studied neurons. Tw...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：
更新日期：1998-08-01 00:00:00
abstract：:Protein phosphorylation represents a major post-translational mechanism through which numerous physiological processes are regulated. In the central nervous system, many extracellular messengers appear to exert their effects by regulating the intracellular concentration of specific second messengers which in turn acti...
journal_title：Neurotoxicology
pub_type： 杂志文章,评审
doi：
更新日期：1994-04-01 00:00:00
abstract：:Environmental exposure to methylmercury (MeHg) during development is of concern because it is easily incorporated in children's body both pre- and post-natal, it acts at several levels of neural pathways (mitochondria, cytoskeleton, neurotransmission) and it causes behavioral impairment in child. We evaluated the effe...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：10.1016/j.neuro.2016.05.018
更新日期：2017-03-01 00:00:00
abstract：:Phthalates are synthetically derived chemicals used as plasticizers in a variety of common household products. They are not chemically bound to plastic polymers and over time, easily migrate out of these products and into the environment. Experimental investigations evaluating the biological impact of phthalate exposu...
journal_title：Neurotoxicology
pub_type： 杂志文章,评审
doi：10.1016/j.neuro.2015.02.008
更新日期：2015-05-01 00:00:00
abstract：:The separate and combined effects of successive administration of amantadine, 100 mg/kg, i.p., and chlorpromazine, 0.2 mg/kg, i.p., on motor activity and whole brain levels of certain biogenic amines and major metabolites were studied in four strains of mice. These were the albino ICR, the inbred BALB/C, C57BL/6 and t...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：
更新日期：1991-10-01 00:00:00
