Neuroprotective effects of docosahexaenoic acid against sub-acute manganese intoxication induced dopaminergic and motor disorders in mice

Fari, Radouane El; Abbaoui, Abdellatif; Bourziq, Anas; Zroudi, Mohamed; Draoui, Ahmed; Khiat, Abdelaati El; Belkouch, Mounir; Elgot, Abdeljalil; Gamrani, Halima

doi:10.1016/j.jchemneu.2019.101686

Cited by 12 publications

(8 citation statements)

References 80 publications

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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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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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“…Rats receiving the high dose of Mn had significantly decreased Rotarod activity, consistent with subacute Mn injections in our earlier observations [ 25 ]. Mn intoxication decreases spontaneous locomotor behavior (open field test) and muscle strength (weight test) [ 11 ]. Mn also induces non-motor behavior deficits such as the memory and recognition deficits in water maze and step-down tests [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

“…The developmental (PND 8–12) exposure to MnCl 2 (5–20 mg/kg) could result in behavioral deficits during adulthood (PND 60–65) [ 33 ]. Thus, behavioral impairments are important aspects of chronic Mn intoxication in humans [ 34 , 35 ] and in experimental animals [ 11 , 25 , 33 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

Chronic Manganese Administration with Longer Intervals Between Injections Produced Neurotoxicity and Hepatotoxicity in Rats

et al. 2020

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Subacute exposure to manganese (Mn) produced Parkinson's disease-like syndrome called Manganism. Chronic onset and progression are characteristics of Manganism, therefore, this study aimed to examine Mn toxicity following chronic exposures. Male Sprague-Dawley rats were injected Mn 2+ 1 and 5 mg/kg, every 10 days for 150 days (15 injections). Animal body weight and behavioral activities were recorded. At the end of experiments, the brain and liver were collected for morphological and molecular analysis. Chronic Mn exposure did not affect animal body weight gain, but the high dose of Mn treatment caused 20% mortality after 140 days of administration. Motor activity deficits were observed in a dose-dependent manner at 148 days of Mn administration. Immunofluorescence double staining of substantia nigra pars compacta (SNpc) revealed the activation of microglia and loss of dopaminergic neurons. The chronic neuroinflammation mediators TNFα, inflammasome Nlrp3, Fc fragment of IgG receptor IIb, and formyl peptide receptor-1 were increased, implicating chronic Mn-induced neuroinflammation. Chronic Mn exposure also produced liver injury, as evidenced by hepatocyte degeneration with pink, condensed nuclei, indicative of apoptotic lesions. The inflammatory cytokines TNFα, IL-1β, and IL-6 were increased, alone with stress-related genes heme oxygenase-1, NAD(P)H:quinone oxidoreductase-1 and metallothionein. Hepatic transporters, such as multidrug resistant proteins (Abcc1, Abcc2, and Abcc3) and solute carrier family proteins (Slc30a1, Slc39a8 and Slc39a14) were increased in attempt to eliminate Mn from the liver. In summary, chronic Mn exposure produced neuroinflammation and dopaminergic neuron loss in the brain, but also produced inflammation to the liver, with upregulation of hepatic transporters.

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“…OF is a square enclosure apparatus with a surface area of 0.5m 2 with a height of 40 cm (50 cm × 50 cm × 40 cm), and the bottom surface is subdivided into 25 identical squares. All mice were habituated to the OF two days before the test [ 33 , 34 ]. On the test day, each mouse was placed in the central area of the OF.…”

Section: Methodsmentioning

confidence: 99%

“…The Rotarod test was used to assess motor coordination in mice and their ability to balance on a 30 mm diameter rotating rod [ 34 ]. Each mouse was placed on the rotating rod (speed of 12 rpm) away from the direction of rotation and 5 min was given to each animal as a maximum time of latency to fall.…”

Section: Methodsmentioning

confidence: 99%

Sensory Motor Function Disturbances in Mice Prenatally Exposed to Low Dose of Ethanol: A Neurobehavioral Study in Postnatal and Adult Stages

Smimih

El‐Mansoury

Saad

et al. 2023

Neurology International

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Prenatal alcohol exposure (PAE) refers to fetal exposure to alcohol during pregnancy through placental barrier transfer from maternal blood. The postnatal outcomes of PAE differ among exposed individuals and range from overt (serious) alcohol-related behavioral and neurophysiological impairments to covert (silenced) symptoms. The aims of the present investigation were to assess the postnatal neurobehavioral disturbances, particularly, motor coordination and sensory-motor function in mice with PAE. Female mice with positive vaginal plugs were divided into three groups: group 1: Et + Pyr: received two i.p injections of ethanol (1 g/kg) followed by pyrazole (100 mg/kg). Group 2: Pyr: received an i.p injection of pyrazole (100 mg/kg). Group 3: C: of saline controls received, in equal volume, saline solution (NaCl 0.9%). After birth, mice pups were weighed and subjected to behavioral tests for motor function screening using the motor ambulation test, cliff aversion, surface righting, and negative geotaxis, while at the adult stage, mice were subjected to the open field, rotarod, parallel bars, and static rods tests. Our data show an obvious decrement of body weight from the first post-natal day (P1) and continues over the adult stage. This was accompanied by an obvious impaired sensory-motor function which was maintained even at the adult stage with alteration of the locomotor and coordination abilities. The current data demonstrate the powerful neurotoxic effect of prenatal ethanol exposure on the sensory-motor and coordination functions, leading to suppose possible structural and/or functional neuronal disturbances, particularly the locomotor network.

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Neuroprotective effects of docosahexaenoic acid against sub-acute manganese intoxication induced dopaminergic and motor disorders in mice

Cited by 12 publications

References 80 publications

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

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

Chronic Manganese Administration with Longer Intervals Between Injections Produced Neurotoxicity and Hepatotoxicity in Rats

Sensory Motor Function Disturbances in Mice Prenatally Exposed to Low Dose of Ethanol: A Neurobehavioral Study in Postnatal and Adult Stages

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