Manganese Inhalation as a Parkinson Disease Model

Ordóñez-Librado, José Luis; Anaya-Martı́nez, Verónica; Gutiérrez-Valdez, Ana Luisa; Colı́n-Barenque, Laura; Montiel-Flores, Enrique; Avila-Costa, Marı́a Rosa

doi:10.4061/2011/612989

Cited by 17 publications

(19 citation statements)

References 95 publications

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“…Special emphasis should be made on the action of Mn 2+ in brain. Inhalation of the mixture of MnCl 2 and Mn(OAc)3 for 5 months developed movement abnormalities, significant loss of substantia nigra compacta (SNc) dopaminergic neurons; these symptoms similar to those observed in Parkinson disease (PD) ( Ordoñez-Librado et al, 2011 ). Dopamine (DA) depletion is closely related to pituitary prolactin biosynthesis.…”

Section: Discussionmentioning

confidence: 70%

Effect of Manganese Exposure on the Reproductive Organs in Immature Female Rats

Kim¹,

Jang²,

Han³

et al. 2012

Development &Amp; Reproduciton

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Manganese (Mn2+) is a trace element that is essential for normal physiology, and is predominantly obtained from food. Several lines of evidence, however, demonstrated that overexposure to MnCl2 exerts serious neurotoxicity, immunotoxicity and developmental toxicity, particularly in male. The present study aimed to evaluate the effect of 0, 1.0, 3.3, and 10 mg/kg/day doses of MnCl2 on the reproductive organs in the immature female rats. Rats (PND 22; S.D. strain) were exposed to MnCl2 (MnCl2 ∙ 4H2O) dissolved in drinking water for 2 weeks. The animals were sacrificed on PND 35, then the tissues were immediately removed and weighed. Histological studies were performed using the uteri tissue samples. Serum LH and FSH levels were measured with the specific ELISA kits. Body weights of the experimental group animals were not significantly different from those of control group animals. However, ovarian tissue weights in 1 mg and 3.3 mg MnCl2 dose groups were significantly lower than those of control animals (p<0.05 and p<0.01, respectively). Uterine tissue weights of 3.3 mg dose MnCl2 groups were significantly lower than those of control animals (p<0.01), while the 1 mg MnCl2 dose and 10 mg MnCl2 dose failed to induce any change in uterine weight. Similarly, only 3.3 mg MnCl2 dose could induce the significant decrease in the oviduct weight compared to the control group (p<0.05). Non-reproductive tissues such as adrenal and kidney failed to respond to all doses of MnCl2 exposure. The uterine histology revealed that the MnCl2 exposure could affect the myometrial cell proliferation particularly in 3.3 mg dose and 10mg dose group. Serum FSH levels were significantly decreased in 1mg MnCl2 dose and 10 MnCl2 mg groups (p<0.05 and p<0.01, respectively). In contrast, treatment with 1 mg MnCl2 dose induced a significant increment of serum LH level (p<0.05). The present study demonstrated that MnCl2 exposure is capable of inducing abnormal development of reproductive tissues, at least to some extent, and altered gonadotropin secretions in immature female rats. Combined with the well-defined actions of this metal on GnRH and prolactin secretion, one can suggest the Mn2+ might be a potential environmental mediator which is involved in the female pubertal process.

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Section: Discussionmentioning

confidence: 70%

Effect of Manganese Exposure on the Reproductive Organs in Immature Female Rats

Kim¹,

Jang²,

Han³

et al. 2012

Development &Amp; Reproduciton

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“…Moreover, our data and others suggest that metal induced PD-like neurological dysfunction independently of the metal exposure route in vivo models [e.g. oral administration (this work), inhalation (Ordoñez-Librado et al 2010) or from aerosolized welding fumes (Sriram et al 2010), intra-peritoneal metal injection (Nakatsuka et al 2009) or intra-cranial metal injection (Ben-Shachar and Youdim 1991) in rats].…”

Section: Discussionmentioning

confidence: 84%

Acute and chronic metal exposure impairs locomotion activity in Drosophila melanogaster: a model to study Parkinsonism

2011

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The biometals iron (Fe), manganese (Mn) and copper (Cu) have been associated to Parkinson's disease (PD) and Parkinsonism. In this work, we report for the first time that acute (15 mM for up to 5 days) or chronic (0.5 mM for up to 15 days) Fe, Mn and Cu exposure significantly reduced life span and locomotor activity (i.e. climbing capabilities) in Drosophila melanogaster. It is shown that the concentration of those biometals dramatically increase in Drosophila's brain acutely or chronically fed with metal. We demonstrate that the metal accumulation in the fly's head is associated with the neurodegeneration of several dopaminergic neuronal clusters. Interestingly, it is found that the PPL2ab DAergic neuronal cluster was erode by the three metals in acute and chronic metal exposure and the PPL3 DAergic cluster was also erode by the three metals but in acute metal exposure only. Furthermore, we found that the chelator desferoxamine, ethylenediaminetetraacetic acid, and D: -penicillamine were able to protect but not rescue D. melanogaster against metal intoxication. Taken together these data suggest that iron, manganese and copper are capable to destroy DAergic neurons in the fly's brain, thereby impairing their movement capabilities. This work provides for the first time metal-induced Parkinson-like symptoms in D. melanogaster. Understanding therefore the effects of biometals in the Drosophila model may provide insights into the toxic effect of metal ions and more effective therapeutic approaches to Parkinsonism.

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“…On the basis of these studies showing the passage of contaminants via the olfactory pathway, some authors have suggested a potential olfactory origin for neurodegenerative diseases . With regards to metals, we can mention the use of manganese inhalation as a model to induce Parkinson's disease in mice . In parallel, another study has shown that olfactory manganese uptake after intranasal administration can influence dopamine transporter and receptors levels in the striatum depending on the iron status of rats .…”

Section: Discussionmentioning

confidence: 99%