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
| Autor: | Colin P. Bloor, Michael T. Williams, Robyn M. Amos-Kroohs, Charles V. Vorhees, Momina A. Qureshi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Agonist
medicine.medical_specialty medicine.drug_class Fenfluramine Health Toxicology and Mutagenesis Iron Transferrin receptor Toxicology Dopamine agonist Open field Article lcsh:RA1190-1270 Internal medicine medicine Amphetamine lcsh:Toxicology. Poisons chemistry.chemical_classification Manganese Iron deficiency medicine.disease Endocrinology chemistry Transferrin Rat Preweaning development medicine.drug |
| Zdroj: | Toxicology Reports, Vol 2, Iss C, Pp 1046-1056 (2015) Toxicology Reports |
| ISSN: | 2214-7500 |
| Popis: | 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 (100mg/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: 5mg/kg), MK-801 (MK801, an NMDA antagonist: 0.2mg/kg), or (+)-amphetamine (AMPH, a dopamine agonist: 1mg/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. |
| Databáze: | OpenAIRE |
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