Beneficial Effect of Deuterated Polyunsaturated Fatty Acids in Rodent Models of Parkinson's Disease and Aging

2019 ◽  
pp. 1800469
Author(s):  
Mikhail S. Shchepinov ◽  
M. Flint Beal ◽  
J. Thomas Brenna ◽  
Noel Y. Calingasan ◽  
Jayandra Chiluwal ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Fatty Acids ◽  
Parkinson's Disease ◽  
Polyunsaturated Fatty Acids ◽  
Beneficial Effect ◽  
Rodent Models

scholarly journals Isotope-reinforced polyunsaturated fatty acids improve Parkinson’s disease-like phenotype in rats overexpressing α-synuclein

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
M. Flint Beal ◽  
Jayandra Chiluwal ◽  
Noel Y. Calingasan ◽  
Ginger L. Milne ◽  
Mikhail S. Shchepinov ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Fatty Acids ◽  
Parkinson's Disease ◽  
Polyunsaturated Fatty Acids ◽  
Mitochondrial Dysfunction ◽  
Hydrogen Abstraction ◽  
Neuronal Loss ◽  
Motor Deficits ◽  
Beneficial Effects ◽  
Neuroprotective Therapy

AbstractLipid peroxidation is a key to a portfolio of neurodegenerative diseases and plays a central role in α-synuclein (α-syn) toxicity, mitochondrial dysfunction and neuronal death, all key processes in the pathogenesis of Parkinson’s disease (PD). Polyunsaturated fatty acids (PUFAs) are important constituents of the synaptic and mitochondrial membranes and are often the first molecular targets attacked by reactive oxygen species (ROS). The rate-limiting step of the chain reaction of ROS-initiated PUFAs autoxidation involves hydrogen abstraction at bis-allylic sites, which can be slowed down if hydrogens are replaced with deuteriums. In this study, we show that targeted overexpression of human A53T α-syn using an AAV vector unilaterally in the rat substantia nigra reproduces some of pathological features seen in PD patients. Chronic dietary supplementation with deuterated PUFAs (D-PUFAs), specifically 0.8% D-linoleic and 0.3% H-linolenic, produced significant disease-modifying beneficial effects against α-syn-induced motor deficits, synaptic pathology, oxidative damage, mitochondrial dysfunction, disrupted trafficking along axons, inflammation and DA neuronal loss. These findings support the clinical evaluation of D-PUFAs as a neuroprotective therapy for PD.

scholarly journals Effect of n-3 polyunsaturated fatty acids on dopaminergic neurons in substantia nigra, brain inflammatory response and behavior in mice with Parkinson’s disease

2021 ◽  
Vol 18 (4) ◽  
pp. 767-772
Author(s):  
Zhaowen Zhang ◽  
Sisi Wang ◽  
Chengyan Li
Keyword(s):  
Parkinson’S Disease ◽  
Fatty Acids ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Inflammatory Response ◽  
Polyunsaturated Fatty Acids ◽  
Normal Control ◽  
Dopaminergic Neurons ◽  
Tnf Α ◽  
Ifn Γ

Purpose: To examine the effect of n-3 polyunsaturated fatty acids (PUFAs) on dopaminergic neurons in substantia nigra, intracerebral inflammatory response and ethology in mice with Parkinson’s disease (PD). Methods: Four groups of male C57BL/6 mice (n = 48) were used: normal control, negative control, n3PUFA, and Madopa groups. Except for normal control group, all groups were given 6- hydroxydopamine hydrochloride (6-OHDA) to establish Parkinson’s mice model. The expressions of tyrosine hydroxylase (TH) and calcium-binding protein (CB) in substantia nigra dopaminergic neurons were determined with immunohistochemistry and Western blot. The contents of nitric oxide (NO), tumor necrosis factor (TNF-α) and interferon γ (IFN-γ) (indices of intracerebral inflammatory response) were measured. Tremor paralysis, moving grid number, standing times, swimming ability, and the number of rollers in each group were observed as indices of ethology. Results: The number of TH and CB-positive neurons in the substantia nigra of n-3PUFA-treated mice was significantly increased, relative to those in Madopa-treated mice (p < 0.05). The expressions of TH and CB proteins in substantia nigra in n-3PUFA group were markedly higher than the corresponding expressions in Madopa-treated mice (p < 0.05). Decreased levels of NO, TNF-α and IFN-γ levels were seen in 3PUFA group, when compared to mice in Madopa group, but higher behavioral scores were obtained in n-3PUFA-treated mice, relative to Madopa-treated mice (p < 0.05). Conclusion: The n-3PUFAs protect substantia nigra compact dopaminergic neurons against Parkinson’s disease, alleviate immune inflammation, and improve the coordination of limb movement. Thus, n-3PUFAs have potential therapeutic application in the management of Parkinson’s disease.

Isotopic reinforcement of essential polyunsaturated fatty acids diminishes nigrostriatal degeneration in a mouse model of Parkinson's disease

2011 ◽  
Vol 207 (2) ◽  
pp. 97-103 ◽  
Author(s):  
Mikhail S. Shchepinov ◽  
Vivian P. Chou ◽  
Erik Pollock ◽  
J. William Langston ◽  
Charles R. Cantor ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Fatty Acids ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Polyunsaturated Fatty Acids ◽  
Nigrostriatal Degeneration

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

2019 ◽  
Vol 121 ◽  
pp. 252-262 ◽  
Author(s):  
Sara Hernando ◽  
Catalina Requejo ◽  
Enara Herran ◽  
Jose Angel Ruiz-Ortega ◽  
Teresa Morera-Herreras ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Fatty Acids ◽  
Parkinson's Disease ◽  
Polyunsaturated Fatty Acids ◽  
Beneficial Effects ◽  
Partial Lesion

Risk of Parkinson's Disease (PD) Associated with the Herbicide Paraquat Is Attenuated by High Dietary Intake of Polyunsaturated Fatty Acids (PUFAs) (S42.004)

Neurology ◽  
2012 ◽  
Vol 78 (Meeting Abstracts 1) ◽  
pp. S42.004-S42.004
Author(s):  
F. Kamel ◽  
G. Richardson ◽  
D. Umbach ◽  
M. Richards ◽  
G. Bhudhikanok ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Fatty Acids ◽  
Parkinson's Disease ◽  
Polyunsaturated Fatty Acids ◽  
Dietary Intake ◽  
High Dietary Intake

scholarly journals Dietary intake and plasma levels of polyunsaturated fatty acids in early-stage Parkinson’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dallah Yoo ◽  
Yunsook Lim ◽  
Yiseul Son ◽  
Hyunkyung Rho ◽  
Chaewon Shin ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Fatty Acids ◽  
Parkinson's Disease ◽  
Polyunsaturated Fatty Acids ◽  
Dietary Intake ◽  
Plasma Levels ◽  
Early Stage ◽  
Plasma Concentrations ◽  
Clinical Severity ◽  
Non Motor Symptoms

AbstractPolyunsaturated fatty acids (PUFA) are important for neuronal function and may contribute to the development of neurodegenerative diseases. Here, we investigated the correlation between dietary intake and plasma concentrations of PUFA and their associations with clinical severity in early-stage Parkinson’s disease (PD). In a case–control study with 38 patients with PD and 33 controls, we assessed dietary intake using food frequency questionnaires and simultaneously measured the plasma levels of five PUFA. No differences were observed in dietary total energy and lipid intake, including PUFA, between patients with PD and controls. However, α-linolenic acid (ALA), linoleic acid (LA), and arachidonic acid (AA) plasma levels were lower in patients with PD. The association between dietary intake and plasma PUFA concentrations was not significant in patients with PD. ALA and LA plasma levels were inversely correlated with motor severity in patients with PD, while docosahexaenoic acid and AA plasma levels were positively correlated with non-motor symptoms after controlling for age and sex.

Impact of oral COMT-inhibitors on gut microbiota and short chain fatty acids in Parkinson's disease

2020 ◽  
Vol 70 ◽  
pp. 20-22 ◽  
Author(s):  
Daniel Grün ◽  
Valerie C. Zimmer ◽  
Jil Kauffmann ◽  
Jörg Spiegel ◽  
Ulrich Dillmann ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Fatty Acids ◽  
Parkinson's Disease ◽  
Gut Microbiota ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Comt Inhibitors ◽  
Chain Fatty Acids

scholarly journals Meta-analysis of the Parkinson’s disease gut microbiome suggests alterations linked to intestinal inflammation

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Stefano Romano ◽  
George M. Savva ◽  
Janis R. Bedarf ◽  
Ian G. Charles ◽  
Falk Hildebrand ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Fatty Acids ◽  
Parkinson's Disease ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Intestinal Inflammation ◽  
Meta Analysis ◽  
Gastrointestinal Symptoms ◽  
Short Chain Fatty Acids ◽  
Inflammatory Status

AbstractThe gut microbiota is emerging as an important modulator of neurodegenerative diseases, and accumulating evidence has linked gut microbes to Parkinson’s disease (PD) symptomatology and pathophysiology. PD is often preceded by gastrointestinal symptoms and alterations of the enteric nervous system accompany the disease. Several studies have analyzed the gut microbiome in PD, but a consensus on the features of the PD-specific microbiota is missing. Here, we conduct a meta-analysis re-analyzing the ten currently available 16S microbiome datasets to investigate whether common alterations in the gut microbiota of PD patients exist across cohorts. We found significant alterations in the PD-associated microbiome, which are robust to study-specific technical heterogeneities, although differences in microbiome structure between PD and controls are small. Enrichment of the genera Lactobacillus, Akkermansia, and Bifidobacterium and depletion of bacteria belonging to the Lachnospiraceae family and the Faecalibacterium genus, both important short-chain fatty acids producers, emerged as the most consistent PD gut microbiome alterations. This dysbiosis might result in a pro-inflammatory status which could be linked to the recurrent gastrointestinal symptoms affecting PD patients.

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