Cargando…

Effects of developmental exposure to manganese and/or low iron diet: Changes to metal transporters, sucrose preference, elevated zero-maze, open-field, and locomotion in response to fenfluramine, amphetamine, and MK-801

Manganese overexposure (MnOE) can be neurotoxic. In humans this can occur through occupational exposure, air or water contamination, well water, soy milk, and some baby formulas. In children MnOE has been associated with cognitive and behavioral deficits. The effects of MnOE may be modified by facto...

Descripción completa

Detalles Bibliográficos
Autores principales: Amos-Kroohs, Robyn M., Bloor, Colin P., Qureshi, Momina A., Vorhees, Charles V., Williams, Michael T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4538693/
https://www.ncbi.nlm.nih.gov/pubmed/26295019
http://dx.doi.org/10.1016/j.toxrep.2015.07.015
_version_ 1782386016632438784
author Amos-Kroohs, Robyn M.
Bloor, Colin P.
Qureshi, Momina A.
Vorhees, Charles V.
Williams, Michael T.
author_facet Amos-Kroohs, Robyn M.
Bloor, Colin P.
Qureshi, Momina A.
Vorhees, Charles V.
Williams, Michael T.
author_sort Amos-Kroohs, Robyn M.
collection PubMed
description Manganese overexposure (MnOE) can be neurotoxic. In humans this can occur through occupational exposure, air or water contamination, well water, soy milk, and some baby formulas. In children MnOE has been associated with cognitive and behavioral deficits. The effects of MnOE may be modified by factors such as iron status. We hypothesized that developmental MnOE would be exacerbated by iron deficiency. A diet with a 90% decrease in iron (FeD) was given to gravid female rats starting on embryonic day 15 and continued through postnatal day (P) 28. Mn (100 mg/kg) or vehicle (VEH) was administered by gavage every other day from P4-28. Metal transporters and receptors (divalent metal transporter-1 (DMT1), transferrin (Tf), transferrin receptor (TfR), and Zrt-Irt-like protein 8 (ZIP8)) were quantified in brain at P28. These markers were increased but the changes were specific: MnOE increased TfR and decreased Tf in hippocampus, whereas FeD increased TfR in neostriatum and increased TfR and DMT1 in the hippocampus, and the combination increased TfR in neostriatum (ZIP8 was unaffected). Identically treated animals were tested behaviorally at P29 or P60. The combination of FeD + MnOE increased head dips in an elevated zero-maze, reversed deficits in sucrose preference induced by MnOE alone, and increased spontaneous locomotion in an open-field. Rats were also evaluated for changes in locomotor activity after challenge with (±)-fenfluramine (FEN, a 5-HT agonist: 5 mg/kg), MK-801 (MK801, an NMDA antagonist: 0.2 mg/kg), or (+)-amphetamine (AMPH, a dopamine agonist: 1 mg/kg). Compared with VEH animals, MnOE animals were more hyperactive after amphetamine or MK-801, and were less inhibited after fenfluramine, regardless of FeD exposure. The results indicate persistent effects of developmental MnOE on brain and behavior but few interactions with dietary iron deficiency.
format Online
Article
Text
id pubmed-4538693
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-45386932016-01-01 Effects of developmental exposure to manganese and/or low iron diet: Changes to metal transporters, sucrose preference, elevated zero-maze, open-field, and locomotion in response to fenfluramine, amphetamine, and MK-801 Amos-Kroohs, Robyn M. Bloor, Colin P. Qureshi, Momina A. Vorhees, Charles V. Williams, Michael T. Toxicol Rep Article Manganese overexposure (MnOE) can be neurotoxic. In humans this can occur through occupational exposure, air or water contamination, well water, soy milk, and some baby formulas. In children MnOE has been associated with cognitive and behavioral deficits. The effects of MnOE may be modified by factors such as iron status. We hypothesized that developmental MnOE would be exacerbated by iron deficiency. A diet with a 90% decrease in iron (FeD) was given to gravid female rats starting on embryonic day 15 and continued through postnatal day (P) 28. Mn (100 mg/kg) or vehicle (VEH) was administered by gavage every other day from P4-28. Metal transporters and receptors (divalent metal transporter-1 (DMT1), transferrin (Tf), transferrin receptor (TfR), and Zrt-Irt-like protein 8 (ZIP8)) were quantified in brain at P28. These markers were increased but the changes were specific: MnOE increased TfR and decreased Tf in hippocampus, whereas FeD increased TfR in neostriatum and increased TfR and DMT1 in the hippocampus, and the combination increased TfR in neostriatum (ZIP8 was unaffected). Identically treated animals were tested behaviorally at P29 or P60. The combination of FeD + MnOE increased head dips in an elevated zero-maze, reversed deficits in sucrose preference induced by MnOE alone, and increased spontaneous locomotion in an open-field. Rats were also evaluated for changes in locomotor activity after challenge with (±)-fenfluramine (FEN, a 5-HT agonist: 5 mg/kg), MK-801 (MK801, an NMDA antagonist: 0.2 mg/kg), or (+)-amphetamine (AMPH, a dopamine agonist: 1 mg/kg). Compared with VEH animals, MnOE animals were more hyperactive after amphetamine or MK-801, and were less inhibited after fenfluramine, regardless of FeD exposure. The results indicate persistent effects of developmental MnOE on brain and behavior but few interactions with dietary iron deficiency. Elsevier 2015-07-19 /pmc/articles/PMC4538693/ /pubmed/26295019 http://dx.doi.org/10.1016/j.toxrep.2015.07.015 Text en © 2015 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Amos-Kroohs, Robyn M.
Bloor, Colin P.
Qureshi, Momina A.
Vorhees, Charles V.
Williams, Michael T.
Effects of developmental exposure to manganese and/or low iron diet: Changes to metal transporters, sucrose preference, elevated zero-maze, open-field, and locomotion in response to fenfluramine, amphetamine, and MK-801
title Effects of developmental exposure to manganese and/or low iron diet: Changes to metal transporters, sucrose preference, elevated zero-maze, open-field, and locomotion in response to fenfluramine, amphetamine, and MK-801
title_full Effects of developmental exposure to manganese and/or low iron diet: Changes to metal transporters, sucrose preference, elevated zero-maze, open-field, and locomotion in response to fenfluramine, amphetamine, and MK-801
title_fullStr Effects of developmental exposure to manganese and/or low iron diet: Changes to metal transporters, sucrose preference, elevated zero-maze, open-field, and locomotion in response to fenfluramine, amphetamine, and MK-801
title_full_unstemmed Effects of developmental exposure to manganese and/or low iron diet: Changes to metal transporters, sucrose preference, elevated zero-maze, open-field, and locomotion in response to fenfluramine, amphetamine, and MK-801
title_short Effects of developmental exposure to manganese and/or low iron diet: Changes to metal transporters, sucrose preference, elevated zero-maze, open-field, and locomotion in response to fenfluramine, amphetamine, and MK-801
title_sort effects of developmental exposure to manganese and/or low iron diet: changes to metal transporters, sucrose preference, elevated zero-maze, open-field, and locomotion in response to fenfluramine, amphetamine, and mk-801
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4538693/
https://www.ncbi.nlm.nih.gov/pubmed/26295019
http://dx.doi.org/10.1016/j.toxrep.2015.07.015
work_keys_str_mv AT amoskroohsrobynm effectsofdevelopmentalexposuretomanganeseandorlowirondietchangestometaltransporterssucrosepreferenceelevatedzeromazeopenfieldandlocomotioninresponsetofenfluramineamphetamineandmk801
AT bloorcolinp effectsofdevelopmentalexposuretomanganeseandorlowirondietchangestometaltransporterssucrosepreferenceelevatedzeromazeopenfieldandlocomotioninresponsetofenfluramineamphetamineandmk801
AT qureshimominaa effectsofdevelopmentalexposuretomanganeseandorlowirondietchangestometaltransporterssucrosepreferenceelevatedzeromazeopenfieldandlocomotioninresponsetofenfluramineamphetamineandmk801
AT vorheescharlesv effectsofdevelopmentalexposuretomanganeseandorlowirondietchangestometaltransporterssucrosepreferenceelevatedzeromazeopenfieldandlocomotioninresponsetofenfluramineamphetamineandmk801
AT williamsmichaelt effectsofdevelopmentalexposuretomanganeseandorlowirondietchangestometaltransporterssucrosepreferenceelevatedzeromazeopenfieldandlocomotioninresponsetofenfluramineamphetamineandmk801