title: Neuroprotective effect of omega-3 polyunsaturated fatty acids in the 6-OHDA model of Parkinson's disease is mediated by a reduction of inducible nitric oxide synthase.
abstract: OBJECTIVE
  Parkinson's disease (PD) is characterized by deterioration of the nigrostriatal system and associated with chronic neuroinflammation. Glial activation has been associated with regulating the survival of dopaminergic neurons and is thought to contribute to PD through the release of proinflammatory and neurotoxic factors, such as reactive nitric oxide (NO) that triggers or exacerbates neurodegeneration in PD. Polyunsaturated fatty acids (PUFAs) exert protective effects, including antiinflammatory, antiapoptotic, and antioxidant activity, and may be promising for delaying or preventing PD by attenuating neuroinflammation and preserving dopaminergic neurons. The present study investigated the effects of fish oil supplementation that was rich in PUFAs on dopaminergic neuron loss, the density of inducible nitric oxide synthase (iNOS)-immunoreactive cells, and microglia and astrocyte reactivity in the substantia nigra pars compacta (SNpc) and striatal dopaminergic fibers.
  
  
  METHODS
  The animals were supplemented with fish oil for 50 days and subjected to unilateral intrastriatal 6-hydroxydopamine (6-OHDA)-induced lesions as a model of PD.
  
  
  RESULTS
  Fish oil mitigated the loss of SNpc neurons and nerve terminals in the striatum that was caused by 6-OHDA. This protective effect was associated with reductions of the density of iNOS-immunoreactive cells and microglia and astrocyte reactivity.
  
  
  CONCLUSIONS
  These results suggest that the antioxidant and antiinflammatory properties of fish oil supplementation are closely related to a decrease in dopaminergic damage that is caused by the 6-OHDA model of PD.
authors.affiliation: a Laboratório de Neurofisiologia, Departamento de Fisiologia , Universidade Federal do Paraná , 81531-990 Curitiba , PR , Brazil.
authors.forename: Marco Aurélio
authors.identifier: http://orcid.org/0000-0003-1231-8756
authors.initials: MA
authors.lastname: Mori
authors.affiliation: a Laboratório de Neurofisiologia, Departamento de Fisiologia , Universidade Federal do Paraná , 81531-990 Curitiba , PR , Brazil.
authors.forename: Ana Marcia
authors.initials: AM
authors.lastname: Delattre
authors.affiliation: a Laboratório de Neurofisiologia, Departamento de Fisiologia , Universidade Federal do Paraná , 81531-990 Curitiba , PR , Brazil.
authors.forename: Bruno
authors.initials: B
authors.lastname: Carabelli
authors.affiliation: a Laboratório de Neurofisiologia, Departamento de Fisiologia , Universidade Federal do Paraná , 81531-990 Curitiba , PR , Brazil.
authors.forename: Claudia
authors.initials: C
authors.lastname: Pudell
authors.affiliation: b Departamento de Morfologia, Fisiologia e Patologia, Escola de Odontologia de Ribeirão Preto (FORP) , Universidade de São Paulo , Av. Café s/n, 14040-904 Ribeirão Preto , SP , Brazil.
authors.forename: Mariza
authors.initials: M
authors.lastname: Bortolanza
authors.affiliation: a Laboratório de Neurofisiologia, Departamento de Fisiologia , Universidade Federal do Paraná , 81531-990 Curitiba , PR , Brazil.
authors.forename: Pedro Vinícius
authors.initials: PV
authors.lastname: Staziaki
authors.affiliation: c Laboratório de Química de Alimentos, Departamento de Química , Universidade Estadual de Maringá , Maringá , PR , Brazil.
authors.forename: Jesuí Vergilio
authors.initials: JV
authors.lastname: Visentainer
authors.affiliation: c Laboratório de Química de Alimentos, Departamento de Química , Universidade Estadual de Maringá , Maringá , PR , Brazil.
authors.forename: Paula Fernandes
authors.initials: PF
authors.lastname: Montanher
authors.affiliation: b Departamento de Morfologia, Fisiologia e Patologia, Escola de Odontologia de Ribeirão Preto (FORP) , Universidade de São Paulo , Av. Café s/n, 14040-904 Ribeirão Preto , SP , Brazil.
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Del Bel
authors.affiliation: a Laboratório de Neurofisiologia, Departamento de Fisiologia , Universidade Federal do Paraná , 81531-990 Curitiba , PR , Brazil.
authors.forename: Anete Curte
authors.initials: AC
authors.lastname: Ferraz
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine; D059290:Dopaminergic Neurons / Q000187:drug effects; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005395:Fish Oils / Q000494:pharmacology; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D009410:Nerve Degeneration / Q000188:drug therapy / Q000209:etiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D016627:Oxidopamine; D010300:Parkinson Disease / Q000188:drug therapy* / Q000209:etiology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D018696:Neuroprotective Agents; D009569:Nitric Oxide; D016627:Oxidopamine; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D004298:Dopamine
keywords: Astrocytes; Dopaminergic neurons; Inducible nitric oxide synthase; Inflammation; Microglia; Neuroprotection; Omega-3; Oxidative stress