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Neuroprotective effects of docosahexaenoic acid against sub-acute manganese intoxication induced dopaminergic and motor disorders in mice.
J Chem Neuroanat. 2019 12; 102:101686.JC

Abstract

Manganese (Mn) is an essential metallic trace element involved in several vital biological functions. Conversely, exposure to excessive levels of Mn induces manganism, causing neurodegeneration and symptoms similar to those seen in Parkinson's disease (PD). Docosahexaenoic acid (DHA) is a long-chain polyunsaturated fatty acid exhibiting neuroprotective properties against neurodegenerative diseases and brain injuries and is known to easily incorporate into membrane phospholipids of brain cells and meditates its corrective actions. In the present study, mice were used for a sub-acute Mn intoxication model to investigate DHA neuroprotective potential against Mn neurotoxicity. We also seek to understand the mechanism by which Mn intoxication induces these motor impairments at 30 mg/kg, by pretreatment with DHA at 200 mg/kg and assessment of changes in spontaneous locomotor behavior by open field test (OF), motor coordination using the rotarod test (RR) and strength by mean of weights test (WT). To highlight these effects on brain neurotransmission, we evaluated the tyrosine hydroxylase immunoreactivity (TH-IR) within substantia nigra compacta (SNC) and striatum (St). Results showed that Mn intoxication significantly altered motor behavior parameters including, decreased of traveled distance by 46%, decreased mean speed by 36%, reduced the ability to sustain the rotarod test to 42%; Moreover, a drop score was obtained using weights test and reflecting affected strength in Mn-intoxicated animals. Pretreatment by DHA prevents mice from Mn toxicity and maintain normal spontaneous activity, motor coordination and strength. Data also showed the ability of Mn to disrupt dopamine neurotransmission by altering tyrosine hydroxylase activity in the nigrostriatal pathway while in pretreated animals, DHA prevented this disruption. Data approved the potential neurotoxic effect of Mn as a risk factor of the Parkinsonism onset, and then demonstrated for the first time the neuroprotective and nutraceutical outcomes of DHA in the sub-acute Mn-intoxication animal model.

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Authors+Show Affiliations

Cadi Ayyad University, Faculty of Sciences Semlalia, Neurosciences, Pharmacology and Environment Unit, Marrakesh, Morocco.

Cadi Ayyad University, Faculty of Sciences Semlalia, Neurosciences, Pharmacology and Environment Unit, Marrakesh, Morocco.

Cadi Ayyad University, Faculty of Sciences Semlalia, Neurosciences, Pharmacology and Environment Unit, Marrakesh, Morocco.

Cadi Ayyad University, Faculty of Sciences Semlalia, Neurosciences, Pharmacology and Environment Unit, Marrakesh, Morocco.

Cadi Ayyad University, Faculty of Sciences Semlalia, Neurosciences, Pharmacology and Environment Unit, Marrakesh, Morocco.

Cadi Ayyad University, Faculty of Sciences Semlalia, Neurosciences, Pharmacology and Environment Unit, Marrakesh, Morocco.

Sorbonne Universités, Université de Technologie de Compiègne, CNRS Enzyme and Cell Engineering Laboratory, Rue Roger Couttolenc, CS 60319, 60203 Compiègne Cedex, France.

Cadi Ayyad University, Faculty of Sciences Semlalia, Neurosciences, Pharmacology and Environment Unit, Marrakesh, Morocco; Unité des Sciences biomédicales, Laboratoire des Sciences et Technologies de la Santé, Institut Supérieur des Sciences de la santé, Université Hassan 1er Settat, Morocco.

Cadi Ayyad University, Faculty of Sciences Semlalia, Neurosciences, Pharmacology and Environment Unit, Marrakesh, Morocco. Electronic address: gamrani@uca.ac.ma.

MeSH

AnimalsBehavior, AnimalCorpus StriatumDisease Models, AnimalDocosahexaenoic AcidsDopamineLocomotionMaleManganeseManganese PoisoningMiceMotor ActivityNeuroprotective AgentsPars CompactaRotarod Performance TestSynaptic TransmissionTyrosine 3-Monooxygenase

Pub Type(s)

Journal Article

Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31562917

Citation

El Fari, Radouane, et al. "Neuroprotective Effects of Docosahexaenoic Acid Against Sub-acute Manganese Intoxication Induced Dopaminergic and Motor Disorders in Mice." Journal of Chemical Neuroanatomy, vol. 102, 2019, p. 101686.

El Fari R, Abbaoui A, Bourziq A, et al. Neuroprotective effects of docosahexaenoic acid against sub-acute manganese intoxication induced dopaminergic and motor disorders in mice. J Chem Neuroanat. 2019;102:101686.

El Fari, R., Abbaoui, A., Bourziq, A., Zroudi, M., Draoui, A., El Khiat, A., Belkouch, M., Elgot, A., & Gamrani, H. (2019). Neuroprotective effects of docosahexaenoic acid against sub-acute manganese intoxication induced dopaminergic and motor disorders in mice. Journal of Chemical Neuroanatomy, 102, 101686. https://doi.org/10.1016/j.jchemneu.2019.101686

El Fari R, et al. Neuroprotective Effects of Docosahexaenoic Acid Against Sub-acute Manganese Intoxication Induced Dopaminergic and Motor Disorders in Mice. J Chem Neuroanat. 2019;102:101686. PubMed PMID: 31562917.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - Neuroprotective effects of docosahexaenoic acid against sub-acute manganese intoxication induced dopaminergic and motor disorders in mice. AU - El Fari,Radouane, AU - Abbaoui,Abdellatif, AU - Bourziq,Anas, AU - Zroudi,Mohamed, AU - Draoui,Ahmed, AU - El Khiat,Abdelaati, AU - Belkouch,Mounir, AU - Elgot,Abdeljalil, AU - Gamrani,Halima, Y1 - 2019/09/25/ PY - 2019/04/29/received PY - 2019/08/22/revised PY - 2019/09/24/accepted PY - 2019/9/29/pubmed PY - 2020/9/15/medline PY - 2019/9/29/entrez KW - DHA KW - Dopamine KW - Locomotor activity KW - Manganese KW - Mice KW - Parkinsonism SP - 101686 EP - 101686 JF - Journal of chemical neuroanatomy JO - J Chem Neuroanat VL - 102 N2 - Manganese (Mn) is an essential metallic trace element involved in several vital biological functions. Conversely, exposure to excessive levels of Mn induces manganism, causing neurodegeneration and symptoms similar to those seen in Parkinson's disease (PD). Docosahexaenoic acid (DHA) is a long-chain polyunsaturated fatty acid exhibiting neuroprotective properties against neurodegenerative diseases and brain injuries and is known to easily incorporate into membrane phospholipids of brain cells and meditates its corrective actions. In the present study, mice were used for a sub-acute Mn intoxication model to investigate DHA neuroprotective potential against Mn neurotoxicity. We also seek to understand the mechanism by which Mn intoxication induces these motor impairments at 30 mg/kg, by pretreatment with DHA at 200 mg/kg and assessment of changes in spontaneous locomotor behavior by open field test (OF), motor coordination using the rotarod test (RR) and strength by mean of weights test (WT). To highlight these effects on brain neurotransmission, we evaluated the tyrosine hydroxylase immunoreactivity (TH-IR) within substantia nigra compacta (SNC) and striatum (St). Results showed that Mn intoxication significantly altered motor behavior parameters including, decreased of traveled distance by 46%, decreased mean speed by 36%, reduced the ability to sustain the rotarod test to 42%; Moreover, a drop score was obtained using weights test and reflecting affected strength in Mn-intoxicated animals. Pretreatment by DHA prevents mice from Mn toxicity and maintain normal spontaneous activity, motor coordination and strength. Data also showed the ability of Mn to disrupt dopamine neurotransmission by altering tyrosine hydroxylase activity in the nigrostriatal pathway while in pretreated animals, DHA prevented this disruption. Data approved the potential neurotoxic effect of Mn as a risk factor of the Parkinsonism onset, and then demonstrated for the first time the neuroprotective and nutraceutical outcomes of DHA in the sub-acute Mn-intoxication animal model. SN - 1873-6300 UR - https://www.unboundmedicine.com/medline/citation/31562917/Neuroprotective_effects_of_docosahexaenoic_acid_against_sub_acute_manganese_intoxication_induced_dopaminergic_and_motor_disorders_in_mice_ DB - PRIME DP - Unbound Medicine ER -