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Maternal Omega-3 Supplement Improves Dopaminergic System in Pre- and Postnatal Inflammation-Induced Neurotoxicity in Parkinson’s Disease Model

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Abstract

Evidence suggests that idiopathic Parkinson’s disease (PD) is the consequence of a neurodevelopmental disruption, rather than strictly a consequence of aging. Thus, we hypothesized that maternal supplement of omega-3 polyunsaturated fatty acids (ω-3 PUFA) may be associated with neuroprotection mechanisms in a self-sustaining cycle of neuroinflammation and neurodegeneration in lipopolysaccharide (LPS)-model of PD. To test this hypothesis, behavioral and neurochemical assay were performed in prenatally LPS-exposed offspring at postnatal day 21. To further determine whether prenatal LPS exposure and maternal ω-3 PUFAs supplementation had persisting effects, brain injury was induced on PN 90 rats, following bilateral intranigral LPS injection. Pre- and postnatal inflammation damage not only affected dopaminergic neurons directly, but it also modified critical features, such as activated microglia and astrocyte cells, disrupting the support provided by the microenvironment. Unexpectedly, our results failed to show any involvement of caspase-dependent and independent apoptosis pathway in neuronal death mechanisms. On the other hand, learning and memory deficits detected with a second toxic exposure were significantly attenuated in maternal ω-3 PUFAs supplementation group. In addition, ω-3 PUFAs promote beneficial effect on synaptic function, maintaining the neurochemical integrity in remaining neurons, without necessarily protect them from neuronal death. Thus, our results suggest that ω-3 PUFAs affect the functional ability of the central nervous system in a complex way in a multiple inflammation-induced neurotoxicity animal model of PD and they disclose new ways of understanding how these fatty acids control responses of the brain to different challenges.

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Acknowledgments

This study was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). The authors are indebted to Laboratório Herbarium Botânico S/A, which kindly donated the fish oil capsules rich in DHA and EPA. ACF is the recipient of Fundação Araucária - Governo do Estado do Paraná fellowship. DS, SMZ, and MMSL are recipients of CNPq fellowship.

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Authors and Affiliations

  1. Laboratório de Neurofisiologia, Setor de Ciências Biológicas, Departamento de Fisiologia, Universidade Federal do Paraná, Av. Francisco H. dos Santos s/n, 81.531 - 990, Curitiba, PR, Brazil

    Ana Marcia Delattre, Bruno Carabelli, Marco Aurélio Mori, Paula G. Kempe, Marcelo M. S. Lima & Anete C. Ferraz

  2. Laboratório de Neurobiologia, Departamento de Patologia Básica, Universidade Federal do Paraná, Curitiba, PR, Brazil

    Luiz E. Rizzo de Souza & Silvio M. Zanata

  3. Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, SP, Brazil

    Ricardo B. Machado & Deborah Suchecki

  4. Laboratório de Neurofisiologia, Departamento de Fisiologia e Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Pernambuco, Recife, Brazil

    Belmira L. S. Andrade da Costa

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  1. Ana Marcia Delattre
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  2. Bruno Carabelli
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  3. Marco Aurélio Mori
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  6. Silvio M. Zanata
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Correspondence to Ana Marcia Delattre or Anete C. Ferraz.

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Delattre, A.M., Carabelli, B., Mori, M.A. et al. Maternal Omega-3 Supplement Improves Dopaminergic System in Pre- and Postnatal Inflammation-Induced Neurotoxicity in Parkinson’s Disease Model. Mol Neurobiol 54, 2090–2106 (2017). https://doi.org/10.1007/s12035-016-9803-8

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