Docosahexaenoic acid protection in a rotenone induced Parkinson's model: Prevention of tubulin and synaptophysin loss, but no association with mitochondrial function

Serrano-García, Norma; Fernández-Valverde, Francisca; Luis-García, Erika Rubí; Granados-Rojas, Leticia; Juárez-Zepeda, Tarsila Elizabeth; Orozco‐Suárez, Sandra; Pedraza‐Chaverrí, José; Orozco-Ibarra, Marisol; Jiménez-Anguiano, Anabel

doi:10.1016/j.neuint.2018.10.015

Cited by 17 publications

(19 citation statements)

References 59 publications

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“…Furthermore, downregulation of the protein leads to activation of apoptotic pathways and was shown in in vivo studies of rotenone effects in rats [33]. Decrease of SYP expression has already been described in in vivo experiments with rotenone treated rats [34]. While Fasudil had no beneficial influence on DAT, MAP2 or TH gene expression under rotenone stress, it significantly reduced the effect of rotenone on SYP and therefore implies a protective effect on the synaptic integrity [35].…”

Section: Effectsmentioning

confidence: 75%

Propionic Acid and Fasudil as Treatment against Rotenone Toxicity in an In Vitro Model of Parkinson’s Disease

et al. 2020

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Parkinson’s disease (PD) is a multifactorial neurodegenerative disease. In recent years, several studies demonstrated that the gastroenteric system and intestinal microbiome influence central nervous system function. The pathological mechanisms triggered thereby change neuronal function in neurodegenerative diseases including dopaminergic neurons in Parkinson´s disease. In this study, we employed a model system for PD of cultured primary mesencephalic cells and used the pesticide rotenone to model dopaminergic cell damage. We examined neuroprotective effects of the Rho kinase inhibitor Fasudil and the short chain fatty acid (SCFA) propionic acid on primary neurons in cell morphological assays, cell survival, gene and protein expression. Fasudil application resulted in significantly enhanced neuritic outgrowth and increased cell survival of dopaminergic cells. The application of propionic acid primarily promoted cell survival of dopaminergic cells against rotenone toxicity and increased neurite outgrowth to a moderate extent. Interestingly, Fasudil augmented gene expression of synaptophysin whereas gene expression levels of tyrosine hydroxylase (TH) were substantially increased by propionic acid. Concerning protein expression propionic acid treatment increased STAT3 levels but did not lead to an increased phosphorylation indicative of pathway activation. Our findings indicate that both Fasudil and propionic acid treatment show beneficial potential in rotenone-lesioned primary mesencephalic cells.

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Section: Effectsmentioning

confidence: 75%

Propionic Acid and Fasudil as Treatment against Rotenone Toxicity in an In Vitro Model of Parkinson’s Disease

et al. 2020

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“…Maternal omega-3 PUFA seem to partially protect a lipopolysaccharide (LPS)-model for PD [68]. Likewise, the omega-3 PUFA DHA protects DA neurons against MPTP–[69,70,71], paraquat—[72] or rotenone-induced toxicity [73] in rodent models and against effects of 6-OHDA-treatment in Caenorhabditis elegans , mice and rats [74,75,76], also when administered as TAG-DHA [77]. Moreover, DHA plays a crucial role in the differentiation of induced pluripotent stem cells (iPSCs) into functional DA neurons [78] and DHA supplementation protects DA neurons from the SN in MPTP-treated mice [79].…”

Section: Fatty Acylsmentioning

confidence: 99%

The Role of Lipids in Parkinson’s Disease

Xicoy

Wieringa

Martens

2019

Cells

179

161

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Parkinson’s disease (PD) is a neurodegenerative disease characterized by a progressive loss of dopaminergic neurons from the nigrostriatal pathway, formation of Lewy bodies, and microgliosis. During the past decades multiple cellular pathways have been associated with PD pathology (i.e., oxidative stress, endosomal-lysosomal dysfunction, endoplasmic reticulum stress, and immune response), yet disease-modifying treatments are not available. We have recently used genetic data from familial and sporadic cases in an unbiased approach to build a molecular landscape for PD, revealing lipids as central players in this disease. Here we extensively review the current knowledge concerning the involvement of various subclasses of fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterols, and lipoproteins in PD pathogenesis. Our review corroborates a central role for most lipid classes, but the available information is fragmented, not always reproducible, and sometimes differs by sex, age or PD etiology of the patients. This hinders drawing firm conclusions about causal or associative effects of dietary lipids or defects in specific steps of lipid metabolism in PD. Future technological advances in lipidomics and additional systematic studies on lipid species from PD patient material may improve this situation and lead to a better appreciation of the significance of lipids for this devastating disease.

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“…Diets enriched in the long-chain omega-3 fatty acids found in fish-and more specifically docosahexaenoic acid (DHA)-have been found to be protective in various rodent models of PD [95][96][97][98][99][100][101][102][103][104][105][106][107]. Decreased expression of inducible NOS, or of nitrite, has been noted in the striatum of PD rodents treated with omega-3s-pointing to suppression of microglia iNOS induction as a likely mechanism for the observed protection [106,107].…”

Section: Blocking Induction Of Inos-ferulic Acid Dha Vitamin D Taumentioning

confidence: 99%

Nutraceuticals Targeting Generation and Oxidant Activity of Peroxynitrite May Aid Prevention and Control of Parkinson’s Disease

McCarty

Lerner

2020

IJMS

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Parkinson’s disease (PD) is a chronic low-grade inflammatory process in which activated microglia generate cytotoxic factors—most prominently peroxynitrite—which induce the death and dysfunction of neighboring dopaminergic neurons. Dying neurons then release damage-associated molecular pattern proteins such as high mobility group box 1 which act on microglia via a range of receptors to amplify microglial activation. Since peroxynitrite is a key mediator in this process, it is proposed that nutraceutical measures which either suppress microglial production of peroxynitrite, or which promote the scavenging of peroxynitrite-derived oxidants, should have value for the prevention and control of PD. Peroxynitrite production can be quelled by suppressing activation of microglial NADPH oxidase—the source of its precursor superoxide—or by down-regulating the signaling pathways that promote microglial expression of inducible nitric oxide synthase (iNOS). Phycocyanobilin of spirulina, ferulic acid, long-chain omega-3 fatty acids, good vitamin D status, promotion of hydrogen sulfide production with taurine and N-acetylcysteine, caffeine, epigallocatechin-gallate, butyrogenic dietary fiber, and probiotics may have potential for blunting microglial iNOS induction. Scavenging of peroxynitrite-derived radicals may be amplified with supplemental zinc or inosine. Astaxanthin has potential for protecting the mitochondrial respiratory chain from peroxynitrite and environmental mitochondrial toxins. Healthful programs of nutraceutical supplementation may prove to be useful and feasible in the primary prevention or slow progression of pre-existing PD. Since damage to the mitochondria in dopaminergic neurons by environmental toxins is suspected to play a role in triggering the self-sustaining inflammation that drives PD pathogenesis, there is also reason to suspect that plant-based diets of modest protein content, and possibly a corn-rich diet high in spermidine, might provide protection from PD by boosting protective mitophagy and thereby aiding efficient mitochondrial function. Low-protein diets can also promote a more even response to levodopa therapy.

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Docosahexaenoic acid protection in a rotenone induced Parkinson's model: Prevention of tubulin and synaptophysin loss, but no association with mitochondrial function

Cited by 17 publications

References 59 publications

Propionic Acid and Fasudil as Treatment against Rotenone Toxicity in an In Vitro Model of Parkinson’s Disease

Propionic Acid and Fasudil as Treatment against Rotenone Toxicity in an In Vitro Model of Parkinson’s Disease

The Role of Lipids in Parkinson’s Disease

Nutraceuticals Targeting Generation and Oxidant Activity of Peroxynitrite May Aid Prevention and Control of Parkinson’s Disease

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