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

Nutr Neurosci. 2018 Jun;21(5):341-351. doi: 10.1080/1028415X.2017.1290928. Epub 2017 Feb 21.

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.

Discussion: 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.

Keywords: Astrocytes; Dopaminergic neurons; Inducible nitric oxide synthase; Inflammation; Microglia; Neuroprotection; Omega-3; Oxidative stress.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants / pharmacology
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Disease Models, Animal
  • Dopamine
  • Dopaminergic Neurons / drug effects
  • Fatty Acids, Omega-3 / pharmacology*
  • Fish Oils / pharmacology
  • Male
  • Microglia / drug effects
  • Microglia / metabolism
  • Nerve Degeneration / drug therapy
  • Nerve Degeneration / etiology
  • Neuroprotective Agents / pharmacology*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism*
  • Oxidopamine
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / etiology
  • Rats
  • Rats, Wistar

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Fatty Acids, Omega-3
  • Fish Oils
  • Neuroprotective Agents
  • Nitric Oxide
  • Oxidopamine
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Dopamine