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

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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