Abstract:
:As a recreational drug of abuse and an injectable anesthetic, ketamine has been shown to cause cognitive dysfunction and induce psychotic states. Although the specific mechanism is still unclear, it may be linked to synaptic receptors, including the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor. Recent evidence suggests that Tau protein phosphorylation and targeted delivery to the postsynaptic area is involved in maintaining neuronal plasticity, indicating that the neurotoxicity induced by ketamine may be related to the transfer of Tau protein after phosphorylation. In this study, we established a model of long-term (6 months) ketamine administration in wild-type (C57BL/6) and Tau knockout mice to investigate the effects of different doses of ketamine administration on Tau protein expression and phosphorylation in the mouse hippocampus. We also investigated changes in AMPA receptor expression in the synaptic membrane of wild-type and Tau knockout mice. Our results showed that long-term ketamine administration led to excessive Tau protein phosphorylation at Ser202/Thr205 and Ser396, but not at Ser199, Ser262 and Ser404. Most importantly, long-term ketamine administration decreased AMPA receptor levels in the hippocampal cell membrane in a Tau protein-dependent manner. Our results reveal the role of Tau protein phosphorylation in the mechanism of ketamine neurotoxicity, suggesting that the changes of membrane AMPA receptor and synaptic function induced by ketamine are mediated by abnormal phosphorylation of Tau protein at specific sites.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Li Y,Ding R,Ren X,Wen G,Dong Z,Yao H,Tan Y,Yu H,Wang X,Zhan X,Yao J,Lu Y,Zhang G,Wu Xdoi
10.1016/j.toxlet.2019.08.023subject
Has Abstractpub_date
2019-10-15 00:00:00pages
107-115eissn
0378-4274issn
1879-3169pii
S0378-4274(19)30237-1journal_volume
315pub_type
杂志文章abstract::The intestinal epithelium is the first barrier against food contaminants and is highly sensitive to Fusarium toxins, especially deoxynivalenol (DON) and zearalenone (ZEA). Here, we explored the effects of low doses of DON and/or ZEA in naturally moldy diets on intestinal functions in piglets, including inflammatory re...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2020.07.032
更新日期:2020-10-15 00:00:00
abstract::Human epidermal keratinocytes which have been cultured were treated with the heavy metal ions of cadmium, mercury, copper and zinc. Cytotoxicity was measured either by protein estimation or by using the neutral red assay. Antioxidants were added in order to find out whether heavy metal-induced cytotoxicity is related ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(94)90170-8
更新日期:1994-04-01 00:00:00
abstract::Inflammation is one of the factors that may increase the sensitivity of hepatic cells to acetaminophen (APAP) induced toxicity. To investigate the mechanisms, we exposed 3-dimensional (3D) Human Liver Microtissues, a co-culture of primary human hepatocytes (PHH) and Kupffer cells (KCs), to 0, 0.5 (low), 5 (median) and...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2019.05.004
更新日期:2019-09-15 00:00:00
abstract::Occupational and environmental exposure to pesticides has been associated with thyroid dysfunction, particularly changes in circulating thyroid hormone levels (T3, T4) and thyroid stimulating hormone (TSH). This study assessed the association between environmental exposure to pesticides and the risk of developing thyr...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2019.08.017
更新日期:2019-10-15 00:00:00
abstract::3-methyladenine DNA glycosylase (AlkD) belongs to a new family of DNA glycosylases; it initiates repair of cytotoxic and promutagenic alkylated bases (its main substrates being 3-methyladenine and 7-methylguanine). The modification of the comet assay (single cell gel electrophoresis) using AlkD enzyme thus allows asse...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2011.10.005
更新日期:2012-01-05 00:00:00
abstract::1,3-Dinitrobenzene (DNB) causes testicular injury, particularly to Sertoli cells, and induces apoptosis in the surrounding germinal cells in rodents; however, the mechanisms causing this toxicity are poorly understood. Our studies, using standard and molecular tools, were conducted to better understand the pathogenesi...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2012.07.010
更新日期:2012-09-03 00:00:00
abstract::Genomic DNA is under continuous assault by various chemical species produced by normal cellular metabolism. In addition, exposure to exogenous agents adds further insult. Modification of DNA by chemical carcinogens has long been recognized as an early event in carcinogenesis and many DNA adducts have been characterize...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/s0378-4274(02)00162-5
更新日期:2002-08-05 00:00:00
abstract::The upregulated α-synuclein (α-syn) and Tau co-occur in methamphetamine (METH) abusers' brains. Here, we designed experiments mainly to investigate whether α-syn and Tau interact in METH exposure. We detected the expression of α-syn, total Tau, and phosphorylation of Tau at Serine 396 (pSer396 Tau) under in vitro and ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2019.11.028
更新日期:2020-02-01 00:00:00
abstract::Chronic feeding of male Wistar rats with food containing hexachlorobenzene (HCB) at 17.5 mmol/kg induced elevation of serum amino-transferases and bilirubin content, increase of microsomal cytochrome P-450 concentration, and decrease of 5'-nucleotidase, K+,Na+- and Mg2+-adenosine triphosphatase activities in liver pla...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(86)90118-9
更新日期:1986-09-01 00:00:00
abstract::In order to study the effect of arsenic on DNA damage, Sprague-Dawley rats were dosed with sodium arsenite (10 mg/kg) with or without 800 microg of benzo(a)pyrene (BP) by intramammilary injection. The animals were sacrificed on day 1, 3, 5, 10 and 27 and the mammary gland tissues were collected for DNA adduct measurem...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(02)00088-7
更新日期:2002-07-07 00:00:00
abstract::Di-(2-propylheptyl) phthalate (DPHP) is used as a plasticizer for polyvinyl chloride products. A tolerable daily intake of DPHP of 0.2 mg/kg body weight has been derived from rat data. Because toxicokinetic data of DPHP in humans were not available, it was the aim of the present work to monitor DPHP and selected metab...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2018.05.010
更新日期:2018-09-15 00:00:00
abstract::Computer simulation can be used to integrate existing toxicity information within a biologically realistic framework. Simulation models calculate relevant measures of target tissue dose based on physiological, biochemical and physicochemical properties and readily support the dose, route, species and interchemical ext...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/0378-4274(89)90029-5
更新日期:1989-12-01 00:00:00
abstract::Propylene oxide (PO) concentrations >or=300 ppm induced cell proliferation and tumors in rat nasal respiratory epithelium (NRE). Cell proliferation was suggested to result from depletion of glutathione (GSH) in NRE. In order to substantiate this hypothesis, cell proliferation - measured by bromodeoxyuridine incorporat...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2009.01.009
更新日期:2009-03-28 00:00:00
abstract::The identification of the no observed adverse effect level (NOAEL) is the key regulatory outcome of toxicity studies. With the introduction of "omics" technologies into toxicological research, the question arises as to how sensitive these technologies are relative to classical regulatory toxicity parameters. BASF SE a...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2014.03.004
更新日期:2014-05-16 00:00:00
abstract::Pregnant rats were exposed to 0, 100, 200, 400 or 800 ppm of carbon disulfide (CS2), 100 ppm of hydrogen sulfide (H2S) alone or in combination with 400 and 800 ppm CS2, 6 h/d during days 6-20 of gestation. Maternal reproduction and fetal parameters were evaluated on gestational day 21. Treatment with 100 or 200 ppm CS...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(89)90186-0
更新日期:1989-07-01 00:00:00
abstract::In humans organophosphorothionate pesticides (OPT) prenatal exposure has been demonstrated. Since OPT-induced neurodevelopmental effects may be due to in situ bioactivation by foetal enzymes, the catalytic activity of the foetal CYP3A7 toward chlorpyrifos (CPF), parathion (PAR), malathion (MAL) and fenthion (FEN) has ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2006.10.006
更新日期:2006-12-15 00:00:00
abstract::Caloric restriction is known to reduce chemically-induced tumor incidence in laboratory animals. The effect is believed to be mediated in part by modification of hepatic drug metabolism, including both phase I and phase II enzymes. Using aflatoxin B1 (AFB1) as a model carcinogen, we studied the effect of caloric restr...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(92)90150-i
更新日期:1992-07-01 00:00:00
abstract::The effect of two herbicides (paraquat and 2,4-dichlorophenoxybutyric acid) and two fungicides (mancozeb and captafol) was studied on the growth of Flagellospora penicillioides, Lunulospora curvula and Phalangispora constricta using the poisoned-food technique. The pesticides did not produce any inhibition of growth a...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(89)90058-1
更新日期:1989-09-01 00:00:00
abstract::The effect of tri- and hexavalent chromium after intraperitoneal administration for 5 consecutive days on testicular histopathology and epididymal sperm number was assessed. Treatment with hexavalent chromium induced testicular atrophy and a reduction in epididymal sperm number after 60 days. No effect was seen after ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(90)90069-x
更新日期:1990-05-01 00:00:00
abstract::Perfluorooctanoic acid (PFOA) is a stable man-made compound with many industrial and commercial uses. Recently, however, concern has been raised that it may induce various toxicological effects such as hepatotoxicity, immunotoxicity, and developmental toxicity. Because levels of circulating microRNAs (miRNAs) can be a...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2013.10.017
更新日期:2014-01-03 00:00:00
abstract::There is sufficient evidence for pulmonary carcinogenicity of inhaled cadmium (Cd) compounds in rats whereas no such evidence was found in mice and hamsters, indicating significant species differences in the pulmonary response to inhaled Cd. We hypothesized that expression of metallothionein (MT) protein in the lung a...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(94)90046-9
更新日期:1994-06-01 00:00:00
abstract::Small molecular weight chemicals may irritate tissues via the induction of the production of various proinflammatory and chemotactic molecules. The structure of these irritants is heterogenous, as is the pattern of their effects. Chemicals are potentially allergenic (i.e. haptens) when they are able to bind proteins s...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/0378-4274(96)03676-4
更新日期:1996-08-01 00:00:00
abstract::Human fetuses and neonates are particularly vulnerable to methylmercury (MeHg)-induced brain damage and are sensitive even to low exposure levels. Previous work of our group evidence that prenatal exposure to MeHg causes cognitive and behavioral alterations and disrupt hippocampus signaling. The current study aimed to...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2017.12.006
更新日期:2018-03-01 00:00:00
abstract::The aim of this study is to predict dermal permeability of four phenolic biocides in four different formulations using a linear solvation energy relationship (LSER) approach, with a calibrated flow through diffusion cell system. Mathematical descriptors were determined in the laboratory, by mathematical computations, ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2007.09.005
更新日期:2007-12-10 00:00:00
abstract::The possible embryotoxic effects of cyclohexylamine hydrochloride doses (expressed as free base) of 10, 30 and 100 mg/kg of body weight per day administered orally in water to mice and rats from the 6th to 15th day post-coitum were investigated. Treatment with daily doses of up to 100 mg/kg of body weight to mice and ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(83)90049-8
更新日期:1983-06-01 00:00:00
abstract::Nonylphenol (NP) is a representative endocrine disruptor that has an adverse effect on male reproduction and posses direct hazard to Sertoli cells, but the mechanism remains incompletely elucidated. In the present study, based on the structural comparability and high affinity between NP and membrane phospholipid molec...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2008.08.011
更新日期:2008-12-15 00:00:00
abstract::To determine whether occupational exposure to trichloroethylene (TCE) influences sympathetic nerve activity, serum dopamine-beta-hydroxylase (DBH) activities were analyzed in 84 male workers exposed to TCE and 83 male age-matched controls. The workers were exposed to about 22 ppm TCE in air. There were no significant ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(90)90187-q
更新日期:1990-12-01 00:00:00
abstract::Di-(2-ethylhexyl)-phthalate (DEHP) is a phthalate ester that binds peroxisome proliferator-activated receptor α (PPARα) to induce proliferation of peroxisomes and regulate the expression of specific target genes. The question of whether the effect of DEHP on female reproductive processes is mediated via PPARα-dependen...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2014.04.019
更新日期:2014-08-04 00:00:00
abstract::Several perfluoroalkyl compounds (PFCs) are ubiquitous environmental contaminants that can biomagnify in species at high trophic levels including wild birds. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) have been detected in wild birds and are known to reduce hatching success of laboratory-expose...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2009.07.004
更新日期:2009-10-28 00:00:00
abstract::The acute toxicity of fullerenol-1 was determined using mice pretreated intraperitoneally (i.p.) with polyhydroxylated C60 derivatives. The LD50 value of fullerenol-1 was estimated to be 1.2 g/kg. Pretreatments with 0.5 and 1.0 g/kg fullerenol-1 decreased cytochromes P450 and b5 contents, and NADPH-cytochrome P450 red...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(97)00071-4
更新日期:1997-09-19 00:00:00