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Title: Gestational lead exposure selectively decreases retinal dopamine amacrine cells and dopamine content in adult mice

Abstract

Gestational lead exposure (GLE) produces supernormal scotopic electroretinograms (ERG) in children, monkeys and rats, and a novel retinal phenotype characterized by an increased number of rod photoreceptors and bipolar cells in adult mice and rats. Since the loss of dopaminergic amacrine cells (DA ACs) in GLE monkeys and rats contributes to supernormal ERGs, the retinal DA system was analyzed in mice following GLE. C57BL/6 female mice were exposed to low (27 ppm), moderate (55 ppm) or high (109 ppm) lead throughout gestation and until postnatal day 10 (PN10). Blood [Pb] in control, low-, moderate- and high-dose GLE was {<=} 1, {<=} 10, {approx} 25 and {approx} 40 {mu}g/dL, respectively, on PN10 and by PN30 all were {<=} 1 {mu}g/dL. At PN60, confocal-stereology studies used vertical sections and wholemounts to characterize tyrosine hydroxylase (TH) expression and the number of DA and other ACs. GLE dose-dependently and selectively decreased the number of TH-immunoreactive (IR) DA ACs and their synaptic plexus without affecting GABAergic, glycinergic or cholinergic ACs. Immunoblots and confocal revealed dose-dependent decreases in retinal TH protein expression and content, although monoamine oxidase-A protein and gene expression were unchanged. High-pressure liquid chromatography showed that GLE dose-dependently decreased retinal DA content, its metabolitesmore » and DA utilization/release. The mechanism of DA selective vulnerability is unknown. However, a GLE-induced loss/dysfunction of DA ACs during development could increase the number of rods and bipolar cells since DA helps regulate neuronal proliferation, whereas during adulthood it could produce ERG supernormality as well as altered circadian rhythms, dark/light adaptation and spatial contrast sensitivity. -- Highlights: Black-Right-Pointing-Pointer Peak [BPb] in control, low-, moderate- and high-dose newborn mice with gestational lead exposure: {<=} 1, {<=} 10, 25 and 40 {mu}g/dL Black-Right-Pointing-Pointer Gestational lead exposure dose-dependently decreased the number of TH-immunoreactive dopaminergic amacrine cells Black-Right-Pointing-Pointer Gestational lead exposure selectively decreased dopaminergic, but not GABAergic, glycinergic or cholinergic, amacrine cells Black-Right-Pointing-Pointer Gestational lead exposure dose-dependently decreased retinal dopamine content, its metabolites and dopamine utilization Black-Right-Pointing-Pointer A decrease in dopamine can alter ERG amplitudes, circadian rhythms, dark/light adaptation and spatial contrast sensitivity.« less

Authors:
 [1];  [2];  [3]; ;  [1]; ;  [4]
  1. Department of Biology and Biochemistry, University of Houston, Houston, TX (United States)
  2. Department of Natural Sciences, University of Houston-Downtown, Houston, TX (United States)
  3. College of Optometry, University of Houston, Houston, TX (United States)
  4. Toxicology and Molecular Biology Branch, Health Effects Research Laboratory, Centers for Disease Control and Prevention-NIOSH, Morgantown, WV USA (United States)
Publication Date:
OSTI Identifier:
22212528
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 256; Journal Issue: 3; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BLOOD; CYTOCHROME OXIDASE; DECARBOXYLASES; DOPA; DOPAMINE; GANGLIONS; HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY; HYDROXYLASES; INFANTS; MICE; RATS; TYROSINE

Citation Formats

Fox, Donald A., E-mail: dafox@uh.edu, Department of Biology and Biochemistry, University of Houston, Houston, TX, Department of Pharmacology and Pharmaceutical Sciences, University of Houston, Houston, TX, Hamilton, W. Ryan, Johnson, Jerry E., Xiao, Weimin, Chaney, Shawntay, Mukherjee, Shradha, Miller, Diane B., and O'Callaghan, James P. Gestational lead exposure selectively decreases retinal dopamine amacrine cells and dopamine content in adult mice. United States: N. p., 2011. Web. doi:10.1016/J.TAAP.2011.05.021.
Fox, Donald A., E-mail: dafox@uh.edu, Department of Biology and Biochemistry, University of Houston, Houston, TX, Department of Pharmacology and Pharmaceutical Sciences, University of Houston, Houston, TX, Hamilton, W. Ryan, Johnson, Jerry E., Xiao, Weimin, Chaney, Shawntay, Mukherjee, Shradha, Miller, Diane B., & O'Callaghan, James P. Gestational lead exposure selectively decreases retinal dopamine amacrine cells and dopamine content in adult mice. United States. https://doi.org/10.1016/J.TAAP.2011.05.021
Fox, Donald A., E-mail: dafox@uh.edu, Department of Biology and Biochemistry, University of Houston, Houston, TX, Department of Pharmacology and Pharmaceutical Sciences, University of Houston, Houston, TX, Hamilton, W. Ryan, Johnson, Jerry E., Xiao, Weimin, Chaney, Shawntay, Mukherjee, Shradha, Miller, Diane B., and O'Callaghan, James P. 2011. "Gestational lead exposure selectively decreases retinal dopamine amacrine cells and dopamine content in adult mice". United States. https://doi.org/10.1016/J.TAAP.2011.05.021.
@article{osti_22212528,
title = {Gestational lead exposure selectively decreases retinal dopamine amacrine cells and dopamine content in adult mice},
author = {Fox, Donald A., E-mail: dafox@uh.edu and Department of Biology and Biochemistry, University of Houston, Houston, TX and Department of Pharmacology and Pharmaceutical Sciences, University of Houston, Houston, TX and Hamilton, W. Ryan and Johnson, Jerry E. and Xiao, Weimin and Chaney, Shawntay and Mukherjee, Shradha and Miller, Diane B. and O'Callaghan, James P.},
abstractNote = {Gestational lead exposure (GLE) produces supernormal scotopic electroretinograms (ERG) in children, monkeys and rats, and a novel retinal phenotype characterized by an increased number of rod photoreceptors and bipolar cells in adult mice and rats. Since the loss of dopaminergic amacrine cells (DA ACs) in GLE monkeys and rats contributes to supernormal ERGs, the retinal DA system was analyzed in mice following GLE. C57BL/6 female mice were exposed to low (27 ppm), moderate (55 ppm) or high (109 ppm) lead throughout gestation and until postnatal day 10 (PN10). Blood [Pb] in control, low-, moderate- and high-dose GLE was {<=} 1, {<=} 10, {approx} 25 and {approx} 40 {mu}g/dL, respectively, on PN10 and by PN30 all were {<=} 1 {mu}g/dL. At PN60, confocal-stereology studies used vertical sections and wholemounts to characterize tyrosine hydroxylase (TH) expression and the number of DA and other ACs. GLE dose-dependently and selectively decreased the number of TH-immunoreactive (IR) DA ACs and their synaptic plexus without affecting GABAergic, glycinergic or cholinergic ACs. Immunoblots and confocal revealed dose-dependent decreases in retinal TH protein expression and content, although monoamine oxidase-A protein and gene expression were unchanged. High-pressure liquid chromatography showed that GLE dose-dependently decreased retinal DA content, its metabolites and DA utilization/release. The mechanism of DA selective vulnerability is unknown. However, a GLE-induced loss/dysfunction of DA ACs during development could increase the number of rods and bipolar cells since DA helps regulate neuronal proliferation, whereas during adulthood it could produce ERG supernormality as well as altered circadian rhythms, dark/light adaptation and spatial contrast sensitivity. -- Highlights: Black-Right-Pointing-Pointer Peak [BPb] in control, low-, moderate- and high-dose newborn mice with gestational lead exposure: {<=} 1, {<=} 10, 25 and 40 {mu}g/dL Black-Right-Pointing-Pointer Gestational lead exposure dose-dependently decreased the number of TH-immunoreactive dopaminergic amacrine cells Black-Right-Pointing-Pointer Gestational lead exposure selectively decreased dopaminergic, but not GABAergic, glycinergic or cholinergic, amacrine cells Black-Right-Pointing-Pointer Gestational lead exposure dose-dependently decreased retinal dopamine content, its metabolites and dopamine utilization Black-Right-Pointing-Pointer A decrease in dopamine can alter ERG amplitudes, circadian rhythms, dark/light adaptation and spatial contrast sensitivity.},
doi = {10.1016/J.TAAP.2011.05.021},
url = {https://www.osti.gov/biblio/22212528}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 3,
volume = 256,
place = {United States},
year = {Tue Nov 15 00:00:00 EST 2011},
month = {Tue Nov 15 00:00:00 EST 2011}
}