Beneficial effects of n-3 polyunsaturated fatty acids administration in a partial lesion model of Parkinson's disease: The role of glia and NRf2 regulation

Neurobiol Dis. 2019 Jan;121:252-262. doi: 10.1016/j.nbd.2018.10.001. Epub 2018 Oct 6.

Abstract

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been widely associated to beneficial effect over different neurodegenerative diseases. In the present study, we tested the potential therapeutic effect of docohexanoic acid (DHA) and its hydroxylated derivate, DHAH, in a partial lesion model of Parkinson's disease (PD). One month before and four months after the striatal lesion with 6-OHDA was made, the animals were daily treated with DHA (50 mg/kg), DHAH (50 mg/kg), vehicle or saline, by intragastric administration. Animal groups under n-3 PUFA treatments exhibited a trend to improve in amphetamine-induced rotations and cylinder test. The beneficial effect seen in behavioral studies were confirmed with TH immunostaining. TH+ fibers and TH+ neurons increased in the experimental groups treated with both n-3 PUFAs, DHA and DHAH. Moreover, the n-3 PUFAs administration decreased the astrogliosis and microgliosis, in both the striatum and substantia nigra (SN), with a higher decrease of GFAP+ and Iba-1+ cells for the DHAH treated group. This experimental group also revealed a positive effect on Nrf2 pathway regulation, decreasing the positive Nrf2 immmunostaining in the striatum and SN, which revealed a potential antioxidant effect of this compound. Taking together, these data suggest a positive effect of n-3 PUFAs administration, and more concretely of DHAH, for PD treatment as it exhibited positive results on dopaminergic system, neuroinflammation and oxidative stress.

Keywords: 6-OHDA; Docohexaenoic acid; Neuroinflammation; Neuroprotection; Parkinson's disease; Polyunsaturated fatty acids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphetamine / administration & dosage
  • Animals
  • Antioxidants / administration & dosage
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism
  • Dopamine / metabolism
  • Dopamine Agents / administration & dosage
  • Dopaminergic Neurons / drug effects*
  • Dopaminergic Neurons / metabolism
  • Fatty Acids, Omega-3 / administration & dosage*
  • Male
  • Motor Activity / drug effects
  • NF-E2-Related Factor 2 / metabolism
  • Neuroglia / drug effects*
  • Neuroglia / metabolism
  • Oxidative Stress / drug effects*
  • Oxidopamine / administration & dosage
  • Parkinson Disease / metabolism*
  • Parkinson Disease / prevention & control
  • Rats, Sprague-Dawley
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Antioxidants
  • Dopamine Agents
  • Fatty Acids, Omega-3
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, rat
  • Oxidopamine
  • Amphetamine
  • Tyrosine 3-Monooxygenase
  • Dopamine