Triglyceride Form of Docosahexaenoic Acid Mediates Neuroprotection in Experimental Parkinsonism.

Maricel Gómez-Soler,Xavier Morató,Joan C Domingo,Francisco Ciruela,Víctor Fernández-Dueñas,Begoña Cordobilla

doi:10.3389/fnins.2018.00604

Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder of unknown etiology. The main treatment of PD consists of medication with dopamine-based drugs, which palliate the symptoms but may produce adverse effects after chronic administration. Accordingly, there is a need to develop novel neuroprotective therapies. Several studies suggest that omega-3 polyunsaturated fatty acids (n-3 PUFA) might provide protection against brain damage. Here, we studied several experimental models of PD, using striatal neuronal cultures, striatal slices, and mice, to assess the neuroprotective effects of docosahexaenoic acid (DHA), the main n-3 PUFA in the brain, administered in its triglyceride form (TG-DHA). Hence, we determined the beneficial effects of TG-DHA on neural viability following 6-hydroxydopamine (6-OHDA)-induced neurotoxicity, a well-established PD model. We also implemented a novel mouse behavioral test, the beam walking test, to finely assess mouse motor skills following dopaminergic denervation. This test showed potential as a useful behavioral tool to assess novel PD treatments. Our results indicated that TG-DHA-mediated neuroprotection was independent of the net incorporation of PUFA into the striatum, thus suggesting a tight control of brain lipid homeostasis both in normal and pathological conditions.

Highlights

Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease, and affects approximately 1% of individuals over the age of 60
We studied the capacity of TG-docosahexaenoic acid (DHA) to reverse 6-OHDA-induced toxicity in striatal primary cultures and striatal slices. 6-OHDA has been widely used to damage dopaminergic neurons in vitro (Ding et al, 2004), we expected to obtain valuable information regarding the Triglyceride of docosahexaenoic acid (TG-DHA) dosages to employ in subsequent experimental models
Having established the 6-OHDA dose and incubation time, we investigated the capacity of TG-DHA to block or attenuate cell death

Summary

Introduction

Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease, and affects approximately 1% of individuals over the age of 60 (de Lau and Breteler, 2006). The main clinical features of PD include asymmetric onset of bradykinesia (slowness to initiate voluntary movements with progressive reduction in speed and amplitude of repetitive actions), rigidity, resting tremor, and posture instability (Meissner et al, 2011). All these symptoms may appear after the selective death of approximately 60% of striatal dopaminergic afferent fibers arising from the substantia nigra pars compacta (Braak and Del Tredici, 2008). Omega-3 & Parkinsonism dopaminergic agonists (Poewe, 2009) This kind of treatment is only palliative, and chronic consumption of dopamine-based drugs may induce a number of adverse effects (i.e., L-DOPA induced dyskinesia) (Huot et al, 2013). Research has focused on going beyond symptomatic treatments in the quest for neuroprotective agents that may impede or delay disease progression

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