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Effects of Preweaning Manganese in Combination with Adult Striatal Dopamine Lesions on Monoamines, BDNF, TrkB, and Cognitive Function in Sprague–Dawley Rats

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Abstract

Manganese (Mn) is an essential nutrient especially during development, but Mn overexposure (MnOE) produces long-term cognitive deficits. Evidence of long-term changes in dopamine in the neostriatum was found in rats from developmental MnOE previously. To examine the relationship between MnOE and dopamine, we tested whether the effects of developmental MnOE would be exaggerated by dopamine reductions induced by 6-hydroxydopamine (6-OHDA) neostriatal infusion when the rats were adults. The experiment consisted of four groups of females and males: Vehicle/Sham, MnOE/Sham, Vehicle/6-OHDA, and MnOE/6-OHDA. Both MnOE/Sham and Vehicle/6-OHDA groups displayed egocentric and allocentric memory deficits, whereas MnOE+6-OHDA had additive effects on spatial memory in the Morris water maze and egocentric learning in the Cincinnati water maze. 6-OHDA reduced dopamine in the neostriatum and nucleus accumbens, reduced norepinephrine in the hippocampus, reduced TH+ cells and TrkB and TH expression in the substantia nigra pars compacta (SNpc), but increased TrkB in the neostriatum. MnOE alone had no effect on monoamines or TrkB in the neostriatum or hippocampus but reduced BDNF in the hippocampus. A number of sex differences were noted; however, only a few significant interactions were found for MnOE and/or 6-OHDA exposure. These data further implicate dopamine and BDNF in the cognitive deficits arising from developmental MnOE.

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Funding

We gratefully acknowledge the following sources of support: the Selma Schottenstein Harris Lab for Research in Parkinson’s, the University of Cincinnati Gardner Family Center for Parkinson’s Disease and Movement Disorders, and the Parkinson’s Disease Support Network-Ohio, Kentucky and Indiana. Additionally, this work was supported by a grant from the University of Cincinnati Gardner Neuroscience Institute-Neurobiology Research Center Pilot Research Program and NIH T32 007051 (RAB).

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  1. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, 45229, USA

    Rebecca A. Bailey, Arnold Gutierrez, Jillian R. Hufgard, Charles V. Vorhees & Michael T. Williams

  2. Division of Neurology, Cincinnati Children’s Research Foundation, Cincinnati, OH, 45229, USA

    Rebecca A. Bailey, Arnold Gutierrez, Jillian R. Hufgard, Charles V. Vorhees & Michael T. Williams

  3. Neuroscience Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA

    Rebecca A. Bailey, Arnold Gutierrez, Tara L. Kyser, Kim B. Seroogy, Charles V. Vorhees & Michael T. Williams

  4. Department of Neurology, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA

    Tara L. Kyser, Ann M. Hemmerle & Kim B. Seroogy

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Bailey, R.A., Gutierrez, A., Kyser, T.L. et al. Effects of Preweaning Manganese in Combination with Adult Striatal Dopamine Lesions on Monoamines, BDNF, TrkB, and Cognitive Function in Sprague–Dawley Rats. Neurotox Res 35, 606–620 (2019). https://doi.org/10.1007/s12640-018-9992-1

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