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Interaction of Curcumin with Manganese May Compromise Metal and Neurotransmitter Homeostasis in the Hippocampus of Young Mice

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Abstract

Manganese (Mn) exposure is related to industrial activities, where absorption by inhalation has high relevance. Manganism, a syndrome caused as a result of excessive accumulation of Mn in the central nervous system, has numerous symptoms similar to those seen in idiopathic Parkinson disease (IPD). Some of these symptoms, such as learning, memory, sensorial, and neurochemical changes, appear before the onset of motor deficits in both manganism and IPD. The aim of this study was to evaluate the possible neuroprotective effects of curcumin against behavioral deficits induced by Mn toxicity in young (2 months old) Swiss mice. We evaluated the effect of chronic inhalation of a Mn mixture [Mn(OAc)3 and MnCl2 (20:40 mM)], 1 h/session, three times a week, over a 14-week period on behavioral and neurochemical parameters. Curcumin was supplemented in the diet (500 or 1,500 ppm in food pellets). The Mn disrupted the motor performance evaluated in the single-pellet reach task, as well as the short- and long-term spatial memory evaluated in the step-down inhibitory avoidance task. Surprisingly, curcumin also produced similar deleterious effects in such behavioral tests. Moreover, the association of Mn plus curcumin significantly increased the levels of Mn and iron, and decreased the levels of dopamine and serotonin in the hippocampus. These alterations were not observed in the striatum. In conclusion, the current Mn treatment protocol resulted in mild deficits in motor and memory functions, resembling the early phases of IPD. Additionally, curcumin showed no beneficial effects against Mn-induced disruption of hippocampal metal and neurotransmitter homeostasis.

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Acknowledgements

The scholarship to AES provided by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) is sincerely appreciated. ALD, MF, EAA, and RDSP are productivity research fellows of CNPq.

Ethics Committee Approval

All procedures in this study were performed in accordance with the NIH Guide for the Care and Use of Laboratory Animals and approved by the local university ethics committee, CEUA.

Conflict of Interest Statement

The authors declare that there are no conflicts of interests.

Funding Sources

This work was supported by CNPq (National Council for Research Development), FINEP Research Grant “Rede Instituto Brasileiro de Neurociência” (IBN-Net #01.06.0842-00), INCT-Excitotoxicity and Neuroprotection and FAPESC (Foundation for the Support of Scientific and Technological Research in the State of Santa Catarina).

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Authors and Affiliations

  1. Department of Biochemistry, Federal University of Santa Catarina, Biological Sciences Centre, 88040-900, Florianópolis, SC, Brazil

    Ariana Ern Schmitz, Luiz F. de Souza, Samara Danielski, Danúbia Bonfanti Santos, Marcelo Farina & Alcir Luiz Dafre

  2. Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, SC, Brazil

    Paulo Alexandre de Oliveira & Rui Daniel Prediger

  3. Department of Chemistry and Environmental Sciences, University Paulista Júlio de Mesquita Filho, São Paulo, SP, Brazil

    Danilo Grünig Humberto da Silva & Eduardo Alves de Almeida

  4. School of Geography, Earth and Environmental Sciences, University of Plymouth, PL4 8AA, Plymouth, UK

    Andrew Fisher

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  1. Ariana Ern Schmitz
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Correspondence to Alcir Luiz Dafre.

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Schmitz, A.E., de Oliveira, P.A., de Souza, L.F. et al. Interaction of Curcumin with Manganese May Compromise Metal and Neurotransmitter Homeostasis in the Hippocampus of Young Mice. Biol Trace Elem Res 158, 399–409 (2014). https://doi.org/10.1007/s12011-014-9951-5

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