Subchronic, Low-Level Intraperitoneal Injections of Manganese (IV) Oxide and Manganese (II) Chloride Affect Rat Brain Neurochemistry

Nielsen, Brian S.; Larsen, Erik Huusfeldt; Ladefoged, Ole; Lam, Henrik Rye

doi:10.1177/1091581817704378

Cited by 10 publications

(6 citation statements)

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“…The authors also investigated whey protein isolate as a protecting factor against these effects as part of their aim to improve outcomes from occupational exposure to heavy metals [ 85 ]. Another animal study using rats found that concentrations of manganese increased in the striatum, altering noradrenaline, dopamine, 5-hydroxytrytamine, glutamate, and acetylcholinesterase concentrations in that area [ 87 ]. Importantly, this study observed rats after low dose, subchronic pesticide exposure far lower than what would usually be considered acute poisoning and more similar to an agricultural worker who may handle pesticides safely enough to experience only low dose exposure [ 87 ].…”

Section: Resultsmentioning

confidence: 99%

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Risk Factors for Brain Health in Agricultural Work: A Systematic Review

Sturm

Castro

Mendez-Colmenares

et al. 2022

IJERPH

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Certain exposures related to agricultural work have been associated with neurological disorders. To date, few studies have included brain health measurements to link specific risk factors with possible neural mechanisms. Moreover, a synthesis of agricultural risk factors associated with poorer brain health outcomes is missing. In this systematic review, we identified 106 articles using keywords related to agriculture, occupational exposure, and the brain. We identified seven major risk factors: non-specific factors that are associated with agricultural work itself, toluene, pesticides, heavy metal or dust exposure, work with farm animals, and nicotine exposure from plants. Of these, pesticides are the most highly studied. The majority of qualifying studies were epidemiological studies. Nigral striatal regions were the most well studied brain area impacted. Of the three human neuroimaging studies we found, two focused on functional networks and the third focused on gray matter. We identified two major directions for future studies that will help inform preventative strategies for brain health in vulnerable agricultural workers: (1) the effects of moderators such as type of work, sex, migrant status, race, and age; and (2) more comprehensive brain imaging studies, both observational and experimental, involving several imaging techniques.

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Section: Resultsmentioning

confidence: 99%

“…The array of neurochemical dysfunction associated with organic solvents exposure manifests as atrophy and memory impairment in the long-term. Animal studies using rats and Drosophila have shown increased dopaminergic degeneration after manganese exposure, which could explain the extrapyramidal symptoms observed in humans [ 85 , 87 ].…”

Section: Discussionmentioning

confidence: 99%

Risk Factors for Brain Health in Agricultural Work: A Systematic Review

Sturm

Castro

Mendez-Colmenares

et al. 2022

IJERPH

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“…47,50 Severe changes in the concentration of different neurotransmitters have been documented in Mn-exposed animals. 51 On the other hand, at the cellular level mitochondria are potential targets of Mn toxicity. 4,5,15,16,20,52-54 Hence, mitochondria protecting agents might serve as potential therapeutic options against Mn cytotoxicity (Figure 1).…”

Section: Discussionmentioning

confidence: 99%

Carnosine Mitigates Manganese Mitotoxicity in an In Vitro Model of Isolated Brain Mitochondria

et al. 2019

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Purpose: Manganese (Mn) is a neurotoxic chemical which induces a wide range of complications in the brain tissue. Impaired locomotor activity and cognitive dysfunction are associated with high brain Mn content. At the cellular level, mitochondria are potential targets for Mn toxicity. Carnosine is a dipeptide abundantly found in human brain. Several pharmacological properties including mitochondrial protecting and antioxidative effects have been attributed to carnosine. The current study aimed to evaluate the effect of carnosine treatment on Mn-induced mitochondrial dysfunction in isolated brain mitochondria. Methods: Mice brain mitochondria were isolated based on the differential centrifugation method and exposed to increasing concentrations of Mn (10 µM-10 mM). Carnosine (1 mM) was added as the protective agent. Mitochondrial indices including mitochondrial depolarization, reactive oxygen species (ROS) formation, mitochondrial dehydrogenases activity, ATP content, and mitochondrial swelling and permeabilization were assessed. Results: Significant deterioration in mitochondrial indices were evident in Mn-exposed brain mitochondria. On the other hand, it was found that carnosine (1 mM) treatment efficiently prevented Mn-induced mitochondrial impairment. Conclusion: These data propose mitochondrial protection as a fundamental mechanism for the effects of carnosine against Mn toxicity. Hence, this peptide might be applicable against Mn neurotoxicity with different etiologies (e.g., in cirrhotic patients).

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“…The first study to evaluate the functional properties of manganese was done by Lin & Koretsky [22]. Since then, MEMRI has been used in different animal models [17,[25][26][27] to evaluate brain circuits controlling different behaviors, using a wide range of doses, MR sequences and image processing [18,[28][29][30][31]. It is well known that chloride manganese in high doses induce toxic effects, mainly in the motor skills of the subjects [25,[28][29][30]32].…”

Section: Introductionmentioning

confidence: 99%

Brain circuits activated by female sexual behavior evaluated by manganese enhanced magnetic resonance imaging

Aguilar-Moreno¹,

Ortíz²,

Concha³

et al. 2022

PLoS ONE

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Magnetic resonance imaging (MRI) allows obtaining anatomical and functional information of the brain in the same subject at different times. Manganese-enhanced MRI (MEMRI) uses manganese ions to identify brain activity, although in high doses it might produce neurotoxic effects. Our aims were to identify a manganese dose that does not affect motivated behaviors such as sexual behavior, running wheel and the rotarod test. The second goal was to determine the optimal dose of chloride manganese (MnCl2) that will allow us to evaluate activation of brain regions after females mated controlling (pacing) the sexual interaction. To achieve that, two experiments were performed. In experiment 1 we evaluated the effects of two doses of MnCl2, 8 and 16 mg/kg. Subjects were injected with one of the doses of MnCl2 24 hours before the test on sessions 1, 5 and 10 and immediately thereafter scanned. Female sexual behavior, running wheel and the rotarod were evaluated once a week for 10 weeks. In experiment 2 we followed a similar procedure, but females paced the sexual interaction once a week for 10 weeks and were injected with one of the doses of MnCl2 24 hours before the test and immediately thereafter scanned on sessions 1, 5 and 10. The results of experiment 1 show that neither dose of MnCl2 induces alterations on sexual behavior, running wheel and rotarod. Experiment 2 demonstrated that MEMRI allow us to detect activation of different brain regions after sexual behavior, including the olfactory bulb (OB), the bed nucleus of the stria terminalis (BNST), the amygdala (AMG), the medial preoptic area (MPOA), the ventromedial hypothalamus (VMH), the nucleus accumbens (NAcc), the striatum (STR) and the hippocampus (Hipp) allowing the identification of changes in brain circuits activated by sexual behavior. The socio sexual circuit showed a higher signal intensity on session 5 than the reward circuit and the control groups indicating that even with sexual experience the activation of the reward circuit requires the activation of the socio sexual circuit. Our study demonstrates that MEMRI can be used repeatedly in the same subject to evaluate the activation of brain circuits after motivated behaviors and how can this activation change with experience.

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Subchronic, Low-Level Intraperitoneal Injections of Manganese (IV) Oxide and Manganese (II) Chloride Affect Rat Brain Neurochemistry

Cited by 10 publications

References 81 publications

Risk Factors for Brain Health in Agricultural Work: A Systematic Review

Risk Factors for Brain Health in Agricultural Work: A Systematic Review

Carnosine Mitigates Manganese Mitotoxicity in an In Vitro Model of Isolated Brain Mitochondria

Brain circuits activated by female sexual behavior evaluated by manganese enhanced magnetic resonance imaging

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