Progress and Prospects in Parkinson's Research/Therapy/Neuroprotection/DHA
DHA offers pointers to new potential forms of neuroprotection.
DHA or Docoaheaenoic acid is an omega-3 fatty acid that is a primary structural component of the human brain, sperm, testicles and retina.
Wang et al  tested the effects of DHA on rats. They found:-
DHA at 5-50 microg/ml successfully protected neurons against the cytotoxicity, markedly increased the cell viability, inhibited both nitric oxide (NO) production and calcium influx, and increased the activities of antioxidant enzymes of glutathione peroxidase (GSH-Px) and glutathione reductase (GR).
Samadi et al  tested the effect of the application of DHA to monkeys treated with MPTP to induce levadopa-induced dyskinesia (LID). Their findings were that :-
These results suggest that DHA can reduce the severity or delay the development of LIDs in a nonhuman primate model of Parkinson's disease.
Cansey et al  worked with rats rendered Parkinsonian by the administration of 6-OHDA. They were then treated with uridine-5’-monophosphate (UMP) and docosahexaenoic acid (DHA).
Rats receiving UMP, DHA, both, or neither, daily, and intrastriatal 6-OHDA 3 days after treatment onset, were tested for d-amphetamine-induced rotational behavior and dopaminergic markers after 24 and 28 days, respectively. UMP/DHA treatment reduced ipsilateral rotations by 57% and significantly elevated striatal dopamine, tyrosine hydroxylase (TH) activity, TH protein and Synapsin-1 on the lesioned side. Hence, giving uridine and DHA may partially restore dopaminergic neurotransmission in this model of Parkinson’s Disease.
Bousquet et al  tested the hypothesis that omega-3 (n-3) polyunsaturated fatty acids (PUFAs) may exert neuroprotective action in Parkinson's disease, by putting mice on a high PUFA diet and then inducing Parkunsonism with MPTP.
The result was a mix of good and bad news but there was sufficient of the former to warrant the conclusion:-
Taken together, these data suggest that a high n-3 PUFA dietary intake exerts neuroprotective actions in an animal model of Parkinsonism.
Ozsoy et al  tested the effect of DHA application on MPTP treated mice . They found that:-
- Docosahexaenoic acid significantly diminished the amount of cell death in the MPTP+DHA group as compared to the MPTP group.
- TBARS levels in the brain were significantly increased following MPTP treatment.
- The activity of brain superoxide dismutase (SOD) was decreased in the MPTP-treated group compared to the control group,
- but DHA treatment did not have an effect on SOD activity in the MPTP+DHA group.
Liu, Xuebo; Shibata, Takahiro; Hisaka, Shinsuke; Kawai, Yoshichika and Osawa, Toshihiko. Full Text J. Clin. Biochem. Nutr. 43 (1): 26–33.
DHA Hydroperoxides as a Potential Inducer of Neuronal Cell Death: a Mitochondrial Dysfunction-Mediated Pathway
Liu, Xuebo; Yamada, Naruomi; Maruyama, Wakako and Osawa, Toshihiko. Full Text J. Biol. Chem. 283 (50): 34887 – 34895.
Formation of Dopamine Adducts Derived from Brain Polyunsaturated Fatty Acids.
Bousquet, Melanie;Gue, Karl; Emond, Vincent; Julien, Pierre; Kang,Jing X.; Cicchetti, Francesca and Calon, Frederic. Full Text J. Lipid Res. 52 (2): 263–271.
Transgenic conversion of omega-6 into omega-3 fatty acids in a mouse model of Parkinson's disease
Kim, Kiyoung; Kim,Song Hee; Kim, Jackwang; Kim, Heuijong and Yim, Jeingbin.Full Text J. Biol. Chem. 287 (9): 6628 – 6641.
Glutathione S-Transferase Omega 1 Activity Is Sufficient to Suppress Neurodegeneration in a Drosophila Model of Parkinson Disease
Use the following links to query the PubMed, PubMed Central and Google Scholar databases using the Search terms:- Parkinson's_Disease DHA.
This will list the latest papers on this topic. You are invited to update this page to reflect such recent results, pointing out their significance.
- Substances with possible neuroprotective properties:
- Caffeine,--Celastrol,--Co-Enzyme Q10,--Creatine,--DHA,--Exendin-4 (EX-4),--GDNF,--Glutathione (GSH),--GM1,--Isradipine,--Melatonin,--Minocycline,--Nicotine,--NSAIDs,--Phenylbutyrate,--Phytic Acid,--Probucol,--Quinoxaline,--Rasagiline,--Riboflavin,--Statins,--Tolcapone,--Urate & Uric Acid,--Vitamin D,--Vitamin E,--
- Wang, X.; Zhao, X.; Mao, Z. Y.; Wang, X. M. and Liu, Z. L. (2003) Abstract Neuroreport. 14 (18):2457 - 2461. Neuroprotective effect of docosahexaenoic acid on glutamate-induced cytotoxicity in rat hippocampal cultures. http://www.ncbi.nlm.nih.gov/pubmed/14663210
- Samadi, P.; Grégoire, L.; Rouillard, C.; Bédard, P,. J.; Di Paolo, T. and Lévesque, D.(2006) Abstract Ann. Neurol. 59 (2):282 - 288. Docosahexaenoic acid reduces levodopa-induced dyskinesias in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine monkeys. http://www.ncbi.nlm.nih.gov/pubmed/16437566
- Cansev, Mehmet; Ulus, Ismail H.; Wang, Lei; Maher, Timothy J.; and Wurtman, Richard J. (2008) Full Text Restorative Effects of Uridine Plus Docosahexaenoic Acid in a Rat Model of Parkinson’s Disease. Neurosci. Res. 62 (3): 206–209. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2592845/?tool=pmcentrez
- Bousquet, M. Saint-Pierre, M.; Julien, C.; Salem, N. Jr.; Cicchetti F. and Calon, F.(2008) Abstract FASEB J. (4):1213 - 1225. Beneficial effects of dietary omega-3 polyunsaturated fatty acid on toxin-induced neuronal degeneration in an animal model of Parkinson's disease. http://www.ncbi.nlm.nih.gov/pubmed/18032633
- Ozsoy, O.; Seval-Celik, Y.; Hacioglu G.: Yargicoglu, P.; Demir, R.; Agar, A. and Aslan, M. (2011) Abstract Neurochem. Int.; 59 (5):664-670.The influence and the mechanism of docosahexaenoic acid on a mouse model of Parkinson's disease. http://www.ncbi.nlm.nih.gov/pubmed/21736911