title: Omega-3 deficiency and neurodegeneration in the substantia nigra: involvement of increased nitric oxide production and reduced BDNF expression.
abstract: BACKGROUND
  Our 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.
  
  
  METHODS
  Second 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.
  
  
  RESULTS
  Increased 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.
  
  
  CONCLUSIONS
  The 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.
  
  
  CONCLUSIONS
  Omega-3 deficiency can reduce the nigrostriatal system's ability to maintain homeostasis under oxidative conditions, which may enhance the risk of Parkinson's disease.
authors.affiliation: Departamento de Fisiologia e Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Pernambuco, Recife, PE, Brazil.
authors.forename: Henriqueta Dias
authors.initials: HD
authors.lastname: Cardoso
authors.affiliation: Departamento de Fisiologia e Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Pernambuco, Recife, PE, Brazil.
authors.forename: Eraldo Fonseca
authors.initials: EF
authors.lastname: dos Santos Junior
authors.affiliation: Departamento de Fisiologia e Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Pernambuco, Recife, PE, Brazil.
authors.forename: David Filipe
authors.initials: DF
authors.lastname: de Santana
authors.affiliation: Departamento de Fisiologia e Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Pernambuco, Recife, PE, Brazil.
authors.forename: Catarina
authors.initials: C
authors.lastname: Gonçalves-Pimentel
authors.affiliation: Departamento de Fisiologia e Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Pernambuco, Recife, PE, Brazil.
authors.forename: Monara Kaélle
authors.initials: MK
authors.lastname: Angelim
authors.affiliation: Departamento de Fisiologia e Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Pernambuco, Recife, PE, Brazil.
authors.forename: Alinny R
authors.initials: AR
authors.lastname: Isaac
authors.affiliation: Núcleo de Educação Física e Ciências do Esporte, Centro Acadêmico de Vitória da Universidade Federal de Pernambuco, Vitória de Santo Antão, PE, Brazil.
authors.forename: Cláudia Jacques
authors.initials: CJ
authors.lastname: Lagranha
authors.affiliation: Departamento de Nutrição, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, Recife, PE, Brazil.
authors.forename: Rubem Carlos Araújo
authors.initials: RC
authors.lastname: Guedes
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Pernambuco, Recife, PE, Brazil.
authors.forename: Eduardo Isidoro
authors.initials: EI
authors.lastname: Beltrão
authors.affiliation: Instituto Internacional de Neurociência de Natal Edmond e Lily Safra, Natal, RN, Brazil.
authors.forename: Edgar
authors.initials: E
authors.lastname: Morya
authors.affiliation: Departamento de Fisiologia e Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Pernambuco, Recife, PE, Brazil.
authors.forename: Marcelo Cairrão Araújo
authors.initials: MC
authors.lastname: Rodrigues
authors.affiliation: Departamento de Fisiologia e Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Pernambuco, Recife, PE, Brazil. Electronic address: bl@ufpe.br.
authors.forename: Belmira Lara da Silveira
authors.initials: BL
authors.lastname: Andrade-da-Costa
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000032:analysis / Q000502:physiology*; D002374:Catalase / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000502:physiology*; D005260:Female; D015227:Lipid Peroxidation; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000209:etiology*; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000502:physiology*; D013482:Superoxide Dismutase / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D015525:Fatty Acids, Omega-3; D009569:Nitric Oxide; D002374:Catalase; D014446:Tyrosine 3-Monooxygenase; D013482:Superoxide Dismutase
keywords: Brain-derived neurotrophic factor; Docosahexaenoic acid; Dopamine; Lipoperoxidation; Oxidative stress; Striatum