Omega-3 deficiency and neurodegeneration in the substantia nigra: Involvement of increased nitric oxide production and reduced BDNF expression |
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Authors: | Henriqueta Dias Cardoso Eraldo Fonseca dos Santos Junior David Filipe de Santana Catarina Gonçalves-Pimentel Monara Kaélle Angelim Alinny R Isaac Cláudia Jacques Lagranha Rubem Carlos Araújo Guedes Eduardo Isidoro Beltrão Edgar Morya Marcelo Cairrão Araújo Rodrigues Belmira Lara da Silveira Andrade-da-Costa |
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Institution: | 1. Departamento de Fisiologia e Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Pernambuco, Recife, PE, Brazil;2. Núcleo de Educação Física e Ciências do Esporte, Centro Acadêmico de Vitória da Universidade Federal de Pernambuco, Vitória de Santo Antão, PE, Brazil;3. Departamento de Nutrição, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, Recife, PE, Brazil;4. Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Pernambuco, Recife, PE, Brazil;5. Instituto Internacional de Neurociência de Natal Edmond e Lily Safra, Natal, RN, Brazil |
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Abstract: | BackgroundOur previous study demonstrated that essential fatty acid (EFA) dietary restriction over two generations induced midbrain dopaminergic cell loss and oxidative stress in the substantia nigra (SN) but not in the striatum of young rats. In the present study we hypothesized that omega-3 deficiency until adulthood would reduce striatum's resilience, increase nitric oxide (NO) levels and the number of BDNF-expressing neurons, both potential mechanisms involved in SN neurodegeneration.MethodsSecond generation rats were raised from gestation on control or EFA-restricted diets until young or adulthood. Lipoperoxidation, NO content, total superoxide dismutase (t-SOD) and catalase enzymatic activities were assessed in the SN and striatum. The number of tyrosine hydroxylase (TH)- and BDNF-expressing neurons was analyzed in the SN.ResultsIncreased NO levels were observed in the striatum of both young and adult EFA-deficient animals but not in the SN, despite a similar omega-3 depletion (~ 65%) in these regions. Increased lipoperoxidation and decreased catalase activity were found in both regions, while lower tSOD activity was observed only in the striatum. Fewer TH- (~ 40%) and BDNF-positive cells (~ 20%) were detected at the SN compared to the control.ConclusionThe present findings demonstrate a differential effect of omega-3 deficiency on NO production in the rat's nigrostriatal system. Prolonging omega-3 depletion until adulthood impaired striatum's anti-oxidant resources and BDNF distribution in the SN, worsening dopaminergic cell degeneration.General significanceOmega-3 deficiency can reduce the nigrostriatal system's ability to maintain homeostasis under oxidative conditions, which may enhance the risk of Parkinson's disease. |
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Keywords: | Brain-derived neurotrophic factor Lipoperoxidation Docosahexaenoic acid Dopamine Oxidative stress Striatum |
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