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 ◽  
...  
2020 ◽  
Vol 8 (1) ◽  
Author(s):  
M. Flint Beal ◽  
Jayandra Chiluwal ◽  
Noel Y. Calingasan ◽  
Ginger L. Milne ◽  
Mikhail S. Shchepinov ◽  
...  

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.


Author(s):  
Mikhail S. Shchepinov ◽  
M. Flint Beal ◽  
J. Thomas Brenna ◽  
Noel Y. Calingasan ◽  
Jayandra Chiluwal ◽  
...  

2021 ◽  
Vol 18 (4) ◽  
pp. 767-772
Author(s):  
Zhaowen Zhang ◽  
Sisi Wang ◽  
Chengyan Li

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.


2011 ◽  
Vol 207 (2) ◽  
pp. 97-103 ◽  
Author(s):  
Mikhail S. Shchepinov ◽  
Vivian P. Chou ◽  
Erik Pollock ◽  
J. William Langston ◽  
Charles R. Cantor ◽  
...  

2021 ◽  
Vol 11 (8) ◽  
pp. 773
Author(s):  
Valentina Leta ◽  
Haidar S. Dafsari ◽  
Anna Sauerbier ◽  
Vinod Metta ◽  
Nataliya Titova ◽  
...  

Device-aided therapies, including levodopa-carbidopa intestinal gel infusion, apomorphine subcutaneous infusion, and deep brain stimulation, are available in many countries for the management of the advanced stage of Parkinson’s disease (PD). Currently, selection of device-aided therapies is mainly focused on patients’ motor profile while non-motor symptoms play a role limited to being regarded as possible exclusion criteria in the decision-making process for the delivery and sustenance of a successful treatment. Differential beneficial effects on specific non-motor symptoms of the currently available device-aided therapies for PD are emerging and these could hold relevant clinical implications. In this viewpoint, we suggest that specific non-motor symptoms could be used as an additional anchor to motor symptoms and not merely as exclusion criteria to deliver bespoke and patient-specific personalised therapy for advanced PD.


Neurology ◽  
2012 ◽  
Vol 78 (Meeting Abstracts 1) ◽  
pp. S42.004-S42.004
Author(s):  
F. Kamel ◽  
G. Richardson ◽  
D. Umbach ◽  
M. Richards ◽  
G. Bhudhikanok ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dallah Yoo ◽  
Yunsook Lim ◽  
Yiseul Son ◽  
Hyunkyung Rho ◽  
Chaewon Shin ◽  
...  

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.


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