Threshold Procedures For Assessing The Impact Of Agents On Brain Reward Systems
Neurosciences & Neurology; Toxicology
Fountain S B; Rowan J D; Ting Y L T
Neurotoxicology and Teratology
1990
1990-09
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/0892-0362(90)90009-2" target="_blank" rel="noreferrer noopener">10.1016/0892-0362(90)90009-2</a>
Transport of a manganese/zinc ethylene-bis-dithiocarbamate fungicide may involve pre-synaptic dopaminergic transporters
C. elegans; Toxicology; Neurosciences & Neurology; parkinsons-disease; exposure; degeneration; costa-rica; pregnant-women; antidepressant; caenorhabditis-elegans; infants environmental-health; leads; Mancozeb; Mancozeb; Manzate; Mn/Zn ethylene-bis-dithiocarbamate; Neurotransmitter transporters; Neurotransmitters
Mancozeb (MZ), an organic-metal fungicide used predominantly on vegetables and fruits, has been linked to neurodegeneration and behavioral disruptions in a variety of organisms, including humans. Both gamma-aminobutyric acid and dopamine neurons appear to be more vulnerable to MZ exposure than other neuronal populations. Based on these observations, we hypothesized that MZ may be differentially transported into these cells through their presynaptic neurotransmitter transporters. To test this, we pretreated Caenorhabditis elegans with transporter antagonists followed by exposure to various concentrations of MZ. Potential neuroprotection was monitored via green fluorescence associated with various neuron populations in transgenic worm strains. Neurodegeneration associated with subacute MZ treatment (30 min) was not altered by transporter antagonist pretreatment. On the other hand, pretreatment with a dopamine transporter antagonist (GBR12909) appeared to protect dopaminergic neurons from chronic (24 h) MZ treatment. These results are consistent with other reports that dopamine transporter levels or activity may modulate toxicity for neurotoxicants.
Montgomery K; Corona C; Frye R; Barnett R; Bailey A; Fitsanakis V A
Neurotoxicology and Teratology
2018
2018-07
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/j.ntt.2018.05.004" target="_blank" rel="noreferrer noopener">10.1016/j.ntt.2018.05.004</a>
Translational Studies on the Role of Developmental Pyrethroid Exposure in ADHD: From Cells to Zebrafish to Mice to Humans and Back Again
Neurosciences & Neurology; Toxicology
Richardson J
Neurotoxicology and Teratology
2017
2017-05
Journal Article
n/a
Triethyltin exposure suppresses synaptic transmission in area CA1 of the rat hippocampal slice.
Female; Animals; Rats; In Vitro Techniques; Synapses/drug effects/*physiology; Evoked Potentials/drug effects; Synaptic Transmission/*drug effects; Hippocampus/drug effects/*pathology/physiology; Pyramidal Tracts/drug effects/*pathology/physiology; Trialkyltin Compounds/*toxicity; Triethyltin Compounds/*toxicity
To examine the effects of TET on the electrophysiology of area CA1 of hippocampus, hippocampal slices were obtained from adult hooded rats and were maintained in vitro using standard techniques. Stimulating and recording electrodes were placed in the Schaffer collaterals and CA1 pyramidal cell body layer, respectively. Following baseline measurements, slices were exposed to either 0, 1, 3, 6, or 10 microM TET in the incubating medium. Both pyramidal cell excitability and recurrent/feedforward inhibition were suppressed in a dose-dependent manner within 3 hr postexposure. The evoked population spike and population excitatory postsynaptic potential (EPSP) were suppressed significantly by 2 hr postexposure for 1 and 3 microM TET exposures, and by 45 min postexposure for 6 and 10 microM exposures. A similar dose-dependency was observed for the suppression of recurrent/feedforward inhibition in hippocampal CA1. A second procedure tested the specificity of TET effects to axonal conduction of Schaffer collaterals. Both the stimulating and recording electrode were placed in the Schaffer collaterals so that both the Schaffer collateral population fiber volley and the CA1 pyramidal cell population EPSP could be recorded. TET exposure suppressed pyramidal cell EPSPs without significantly affecting the amplitude of Schaffer collateral fiber volleys. The results support the view that acute TET exposure suppresses synaptic transmission in area CA1 of hippocampus.
Fountain S B; Ting Y L; Hennes S K; Teyler T J
Neurotoxicology and teratology
1988
1988-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0892-0362(88)90090-6" target="_blank" rel="noreferrer noopener">10.1016/0892-0362(88)90090-6</a>
Methamphetamine-gonadal steroid hormonal interactions: effects upon acute toxicity and striatal dopamine concentrations.
Female; Male; Animals; Mice; Sex Factors; Body Weight/drug effects; Organ Size/drug effects; Dopamine/*metabolism; Body Temperature/drug effects; Methamphetamine/*toxicity; Corpus Striatum/*metabolism; Orchiectomy; Ovariectomy; Drug Interactions; Estrogens/pharmacology/*physiology; Heart Rate/drug effects; Heart Ventricles/metabolism; Norepinephrine/metabolism; Pituitary Gland/anatomy & histology; Testosterone/pharmacology/*physiology; Inbred Strains
Methamphetamine (MA)-related deaths and nigrostriatal dopaminergic (NSDA) neurotoxicity are greater in males. The exact basis for this gender difference is not known, but data, which show that estrogen (E) can function as a protectant of both the cardiovascular and NSDA systems, suggest an important role for gonadal steroids in modulating toxicity to this psychostimulant. In the present report, we examined the effects of treatment with the gonadal steroid hormones E and testosterone (T) upon MA-induced toxicity within intact and castrated female and male CD-1 mice. Treatment of intact males with E produced a severe acute toxicity to MA, with only 41% (7/17) males surviving at 24-h post-MA. This incidence of mortality was significantly different from that of nonhormonally treated mice receiving an identical regimen of MA [94% survival (16/17)]. None of the other treatment groups showed mortality rates, which differed significantly from the nonhormonally treated mice. Striatal dopamine (DA) concentrations of E-treated female mice (intact or castrated) were significantly greater than that of the nonhormonally treated mice, which failed to differ statistically among each other. In an attempt to understand some of the bases for the mortality rates in
Dluzen Dean E; Anderson Linda I; Pilati Charles F
Neurotoxicology and teratology
2002
2002-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Markers associated with testosterone enhancement of methamphetamine-induced striatal dopaminergic neurotoxicity.
Animals; Biomarkers/metabolism; Blotting; Body Temperature/drug effects; Body Weight/drug effects; Corpus Striatum/*drug effects/metabolism; Dopamine Plasma Membrane Transport Proteins/metabolism; Dopamine/*metabolism; Drug Synergism; HSP70 Heat-Shock Proteins/metabolism; Inbred Strains; Male; Methamphetamine/*toxicity; Mice; Neurotoxicity Syndromes/*etiology/metabolism; Oxidative Stress/drug effects; Testosterone Propionate/*pharmacology; Vesicular Monoamine Transport Proteins/metabolism; Western
Intact male CD-1 mice received an injection of testosterone propionate (TP–5 ug), progesterone (P–5 mg), the oil vehicle or remained untreated (control). At 24 hours after hormonal treatments the mice received an injection of methamphetamine (MA–40 mg/kg) and rectal temperatures were measured. At 5 days post-MA, assays were performed to assess effects of these treatments. Maximal increases in body temperatures, that were significantly greater than oil-treated controls, were obtained in TP-treated mice. At 5 days post-MA, maximal weight reductions were obtained with TP-treated mice, while P-treated mice showed no significant decrease between the pre- versus post-MA determinations. Striatal dopamine concentrations showed maximal reductions and heat-shock protein-70 maximal increases in the TP group, with both differing significantly as compared with all other groups. Protein levels of dopamine transporters were significantly decreased in P-treated mice, while vesicular monoamine transporter-2 was significantly decreased in TP-treated mice. Taken together, these results suggest that testosterone exacerbates the deleterious effects of MA within male mice as indicated by a number of markers related to neurotoxicity. The changes in markers as associated with this enhanced neurotoxicity suggest that TP may increase thermal/energy responses and/or oxidative stress to produce this effect.
Buletko A Blake; Dluzen Dean E; McDermott Janet L; Darvesh Altaf S; Geldenhuys Werner J
Neurotoxicology and teratology
2012
2012-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.ntt.2012.03.003" target="_blank" rel="noreferrer noopener">10.1016/j.ntt.2012.03.003</a>
Sex differences in methamphetamine-evoked striatal dopamine of mice are reversed by nomifensine.
*Sex Characteristics; Animals; Corpus Striatum/*drug effects; Dopamine Agents/pharmacology; Dopamine Uptake Inhibitors/*pharmacology; Dopamine/*metabolism; Drug Interactions; Female; Male; Methamphetamine/pharmacology; Mice; Nomifensine/*pharmacology; Potassium/pharmacology
Male mice show more severe striatal dopamine depletions to the psychostimulant, methamphetamine (MA). To gain some understanding for this sex difference, we examined MA-evoked dopamine (DA) responses from superfused striatal tissue fragments of male and female mice under conditions of a dopamine transporter which was either unaltered (Experiment 1) or inhibited, with use of the drug, nomifensine (Experiment 2). In Experiment 1, MA-evoked DA was significantly greater in male versus female mice. In Experiment 2, diminished, albeit statistically significant, DA responses to MA infusion in the presence of nomifensine were obtained from striatal tissue of female, but not male, mice. In Experiment 3, potassium-evoked DA responses and sex differences were abolished in the presence of nomifensine. These data demonstrate a clear sex difference in DA responses to MA. Interestingly, under conditions where dopamine transporter function is inhibited, MA retains its ability to evoke DA. However, this capacity was only observed within striatal tissue fragments of female mice and not under conditions of potassium-evoked DA. These results indicate an additional component for the bases of sex differences in nigrostriatal dopaminergic function in health and in disease. In particular, the present findings have important implications in suggesting an alternative, non-traditional, mechanism for MA effects and indicate that such a function is limited to females.
Kunnathur Vidhya; Shemisa Kamal; Liu Bin; Salvaterra Ty J; Dluzen Dean E
Neurotoxicology and teratology
2006
2006-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.ntt.2006.07.001" target="_blank" rel="noreferrer noopener">10.1016/j.ntt.2006.07.001</a>
Estrogen as a neuroprotectant against MPTP-induced neurotoxicity in C57/B1 mice.
*MPTP Poisoning; Animals; Corpus Striatum/drug effects/*metabolism/pathology; Dopamine/*metabolism; Drug Implants; Estradiol/administration & dosage/*pharmacology; Female; Inbred C57BL; Male; Mice; Neuroprotective Agents/administration & dosage/*pharmacology; Neurotoxins; Olfactory Pathways/drug effects/*metabolism/pathology; Orchiectomy; Ovariectomy; Sex Characteristics
Castrated retired breeder male and female mice were treated or not with a 17 beta-estradiol pellet. At 10 days postcastration +/- estrogen treatment all animals were treated with MPTP. Five days later, concentrations of dopamine were determined from the corpus striatum and olfactory tubercle. Both castrated male and female mice treated with estrogen had significantly greater concentrations of dopamine within the corpus striatum compared with their respective gender controls, which did not receive estrogen. By contrast, no statistically significant differences in olfactory tubercle dopamine concentrations were obtained. Overall concentrations of dopamine within the corpus striatum, but not olfactory tubercle, were substantially greater in female vs. male mice. These data demonstrate that treatment with estrogen prevents reductions in corpus striatal dopamine concentrations in castrated mice treated with MPTP. Interestingly, this effect of estrogen was observed in both male and female mice. These results suggest that estrogen may serve as a neuroprotectant against an agent that is toxic to the nigrostriatal dopaminergic system in both male and female animal models of Parkinsonism.
Dluzen D E; McDermott J L; Liu B
Neurotoxicology and teratology
1996
1996-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0892-0362(96)00086-4" target="_blank" rel="noreferrer noopener">10.1016/0892-0362(96)00086-4</a>