Abstract:
:The indirubins long have been used in Chinese medicine for treatment of myelocytic leukemia. Among the many more recently described biological activities of the indirubins, attention has been directed toward the ability of these compounds to inhibit GSK-3 and CDKs, kinases implicated in neurodegenerative conditions. Little information is available on effects of indirubins on chemically-induced neurodegeneration. Here we examined the influence of three indirubins on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- and kainic acid (KA)-induced neurotoxicity in the mouse. The three indirubins examined were 6-bromoindirubin-3'-oxime (6BIO), 5-bromoindirubin-3'-oxime (5BIO) and 5-amino-6-bromoindirubin (5A6BI). The first two derivatives were previously described indirubins with low nanomolar inhibitory activity against GSK-3 and CDKs. The third compound was synthesized by the dimerization of 5-amino-6-bromoisatin with 3-acetoxyindol. The synthesis of the key compound 5-amino-6-bromoisatin was based on the bromination of the ketal of 5-amino-isatin. All indirubins examined decreased various measures associated with dopaminergic neurotransmission in striatum. These effects occurred alone or over and above the decrements seen following administration of the dopaminergic neurotoxicant, MPTP. Striatal serotonin and serotonin turnover were decreased by the indirubins in MPTP-treated mice. None of these striatal effects of the indirubins alone were associated with evidence of astrogliosis, an indicator of underlying neuropathology, nor did they potentiate the astrogliosis accompanying administration of MPTP. In general, the indirubins reduced KA-associated mortality and striatal but not hippocampal astrogliosis due to this toxicant. The data suggest that indirubins affect striatal biogenic amine levels and turnover in intact mice. The data do not indicate a neuroprotective action of indirubins in mice treated with MPTP but that they do suggest that they may be neuroprotective against KA-induced injury of the neostriatum.
journal_name
Neurotoxicol Teratoljournal_title
Neurotoxicology and teratologyauthors
Magiatis P,Polychronopoulos P,Skaltsounis AL,Lozach O,Meijer L,Miller DB,O'Callaghan JPdoi
10.1016/j.ntt.2009.12.005subject
Has Abstractpub_date
2010-03-01 00:00:00pages
212-9issue
2eissn
0892-0362issn
1872-9738pii
S0892-0362(09)00223-2journal_volume
32pub_type
杂志文章abstract::Visual thresholds for luminance increments were obtained behaviorally and electrophysiologically from rats exposed to a polychlorinated biphenyl (PCB) during development. Male Long-Evans rats exposed to 0, 0.25, or 1.0 microg/kg/day of 3,3',4,4', 5-pentachlorobiphenyl (PCB 126) through gestation and weaning were train...
journal_title:Neurotoxicology and teratology
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abstract::Pregnant Long-Evans rats were fed a liquid diet containing either 35% ethanol-derived calories (group E) or were pair-fed to group E dams using the same diet with an equivalent amount of sucrose-derived calories (group PFC) on days 7-18 of gestation. At birth half the litters were fostered to other dams of the same tr...
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journal_title:Neurotoxicology and teratology
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abstract::The potential of emamectin benzoate (EB) to cause developmental neurotoxicity in Sprague-Dawley rats was assessed using a study design by the US EPA. Dosages of 0 (deionized water), 0.1, 0.6, or 3.6 mg/kg/day were administered at 5 ml/kg by oral gavage from gestational day (GD) 6 to lactational day (LD) 20 to groups o...
journal_title:Neurotoxicology and teratology
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abstract::4-Nonylphenol (4-NP), an estrogen mimicking compound is produced by biodegradation of alkylethoxylates. It is well established that 4-NP can affect the development of aquatic animals by disrupting the endocrine signals. Here we show for the first time in zebrafish that 4-NP does not only target the neuroendocrine syst...
journal_title:Neurotoxicology and teratology
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journal_title:Neurotoxicology and teratology
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doi:10.1016/j.ntt.2006.06.006
更新日期:2006-09-01 00:00:00
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journal_title:Neurotoxicology and teratology
pub_type: 杂志文章,评审
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abstract:BACKGROUND:Exposures to hydrogen sulfide gas (H2S) have been inconclusively linked to a variety of negative cognitive outcomes. We investigated possible effects on cognitive function in an urban population with chronic, low-level exposure to H2S. METHODS:Participants were 1637 adults, aged 18-65 years from Rotorua cit...
journal_title:Neurotoxicology and teratology
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doi:10.1016/j.ntt.2014.02.002
更新日期:2014-03-01 00:00:00
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journal_title:Neurotoxicology and teratology
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abstract::Pregnant albino rats received 2 IP injections, spaced by 4 h, of either ethanol (2.9 g/kg in 24% v/v saline solution) or saline, on gestational day (GD) 8. During adulthood, male rats prenatally exposed to alcohol exhibited an increased stereotyped behavioral response to 12 mg/kg of amphetamine (AMPH) or 1 mg/kg of ap...
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pub_type: 杂志文章
doi:10.1016/0892-0362(93)90007-b
更新日期:1993-07-01 00:00:00
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journal_title:Neurotoxicology and teratology
pub_type: 杂志文章,评审
doi:10.1016/j.ntt.2007.02.003
更新日期:2007-07-01 00:00:00
abstract::The therapeutic use in the human teratogenic range of retinoid compounds (Accutane; Tigason) for the treatment of dermatologic disorders has refocused attention on the teratogenicity of vitamin A-related compounds. This article reviews rodent data on three retinoids: vitamin A (retinol), all-trans retinoic acid (treti...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章,评审
doi:10.1016/0892-0362(93)90015-g
更新日期:1993-05-01 00:00:00
abstract::This population-based retrospective cohort study examined Structural Magnetic Resonance Imaging (MRI) of the brain in relation to prenatal and early postnatal exposure to tetrachloroethylene (PCE)-contaminated drinking water on Cape Cod, Massachusetts. Subjects were identified through birth records from 1969 through 1...
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doi:10.1016/j.ntt.2013.03.060
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journal_title:Neurotoxicology and teratology
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abstract::The increased use of cocaine in the United States and worldwide has created great concern about its effects on fetuses and neonates of pregnant cocaine abusers. The effects on neonates are varied: fetal growth delay, microcephaly, abnormal neurological functions, microphthalmia, and maternal obstetric complications. I...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/s0892-0362(96)00227-9
更新日期:1997-05-01 00:00:00
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journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/s0892-0362(00)00094-5
更新日期:2000-09-01 00:00:00
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journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/0892-0362(90)90112-p
更新日期:1990-01-01 00:00:00
abstract::Dysmorphologic and anthropometric assessments were performed on 154 6-year-old children prenatally exposed to cocaine (PCE) and 131 high-risk controls (NCE) of similar race and social class. Adjusted mean height z scores demonstrated a dose-response with metahydroxybenzoylecgonine above a threshold of 100 ng/g of meco...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/j.ntt.2005.09.003
更新日期:2006-01-01 00:00:00
abstract::Inhalation exposure of male and female Fischer 344 rats to sulfuryl fluoride [Vikane (Dow Chemical Company) gas fumigant] at 300 ppm for 6 hr/day, 5 days week, for 13 weeks caused diminished weight gain, dental fluorosis, a slight decrease in grooming, decreased flicker fusion threshold, slowing of flash, auditory and...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
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更新日期:1988-03-01 00:00:00
abstract::Gestational Toluene Exposure Effects on Spontaneous and Amphetamine-Induced Locomotor Behavior in Rats. Bowen, S.E., Mohammadi, M.H., Batis, J.C., and Hannigan, J.H. Neurotoxicology and Teratology, XX, 2006. The abuse of volatile organic solvents (inhalants) continues to be a major health concern throughout the world....
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/j.ntt.2006.09.027
更新日期:2007-03-01 00:00:00
abstract:OBJECTIVE:A number of studies suggest that Pb exposure increases cardiovascular disease risk in humans. As a potential mechanism for this effect, we recently reported a significant association between early childhood Pb levels and cardiovascular response to acute stress. The current study considers the association betw...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/j.ntt.2010.10.001
更新日期:2011-03-01 00:00:00
abstract::Most behavioral teratology studies have focused on pharmaceutical agents. Investigations of developmental toxicity are lacking for the majority of the nearly 100,000 industrial chemicals currently in use. Only some three dozen chemicals have been examined for behavioral/neurochemical deviations in offspring following ...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章,评审
doi:10.1016/0892-0362(90)90047-g
更新日期:1990-07-01 00:00:00
abstract::Perfluorinated alkyls are widely-used agents that accumulate in ecosystems and organisms because of their slow rate of degradation. There is increasing concern that these agents may be developmental neurotoxicants and the present study was designed to develop an avian model for the neurobehavioral teratogenicity of pe...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/j.ntt.2009.11.004
更新日期:2010-03-01 00:00:00