The effect of manganese exposure in Atp13a2-deficient mice

Fleming, Sheila M.; Santiago, Nicholas A.; Mullin, Elizabeth J.; Pamphile, Shanta; Karkare, Swagata; Lemkuhl, Andrew; Ekhator, Osunde R.; Linn, Stephen C.; Holden, John G.; Aga, Diana S.; Roth, Jerome A.; Liou, Benjamin; Sun, Ying; Shull, Gary E.; Schultheis, Patrick J.

doi:10.1016/j.neuro.2017.06.005

Cited by 22 publications

(25 citation statements)

References 68 publications

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“…[29][30][31] Briefly, the beam consists of four sections (25 cm each, 1 m total length) with each section having a different width. [29][30][31] Briefly, the beam consists of four sections (25 cm each, 1 m total length) with each section having a different width.…”

Section: Motor Behavioral Analysesmentioning

confidence: 99%

“…[29][30][31] The cylinder was placed on a piece of glass with a mirror positioned at an angle beneath the glass to allow a clear view of movements along the ground and walls of the cylinder. [29][30][31] The cylinder was placed on a piece of glass with a mirror positioned at an angle beneath the glass to allow a clear view of movements along the ground and walls of the cylinder.…”

Section: Motor Behavioral Analysesmentioning

confidence: 99%

“…[29][30][31] On the challenging beam, mice are tested for the time it takes to cross the beam and how many errors were committed while crossing. First, mice were tested on the challenging beam, a raised beam that reduces in width as it gets closer to the platform.…”

Section: Pharmacological Inhibition Of Csf1r Attenuates Mptp-inducementioning

confidence: 99%

“…Motor performance and coordination were determined by the challenging beam traversal task and performed as previously described. [29][30][31] Briefly, the beam consists of four sections (25 cm each, 1 m total length) with each section having a different width. The beam width begins at 3.5 cm and gradually narrows to 0.5 cm by 1 cm increments.…”

Section: Motor Behavioral Analysesmentioning

confidence: 99%

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Pharmacological inhibition of CSF1R by GW2580 reduces microglial proliferation and is protective against neuroinflammation and dopaminergic neurodegeneration

et al. 2019

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Increased pro-inflammatory cytokine levels and proliferation of activated microglia have been found in Parkinson's disease (PD) patients and animal models of PD, suggesting that targeting of the microglial inflammatory response may result in neuroprotection in PD. Microglial proliferation is regulated by many factors, but colony stimulating factor-1 receptor (CSF1R) has emerged as a primary factor. Using data mining techniques on existing microarray data, we found that mRNA expression of the CSF1R ligand, CSF-1, is increased in the brain of PD patients compared to controls. In two different neurotoxic mouse models of PD, acute MPTP and sub-chronic LPS treatment, mRNA and protein levels of CSF1R and CSF-1 were significantly increased. Treatment with the CSF1R inhibitor GW2580 significantly attenuated MPTP-induced CSF1R activation and Iba1-positive cell proliferation, without a reduction of the basal Iba1-positive population in the substantia nigra. GW2580 treatment also significantly decreased mRNA levels of pro-inflammatory factors, without alteration of anti-inflammatory mediators, and significantly attenuated the MPTPinduced loss of dopamine neurons and motor behavioral deficits. Importantly, these effects were observed in the absence of overt microglial depletion, suggesting that targeting CSF1R signaling may be a viable neuroprotective strategy in PD that disrupts pro-inflammatory signaling, but maintains the beneficial effects of microglia. K E Y W O R D Smicroglia, neuroprotection, Parkinson's disease, proliferation 1680 |

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Section: Motor Behavioral Analysesmentioning

confidence: 99%

Section: Motor Behavioral Analysesmentioning

confidence: 99%

Section: Pharmacological Inhibition Of Csf1r Attenuates Mptp-inducementioning

confidence: 99%

Section: Motor Behavioral Analysesmentioning

confidence: 99%

See 2 more Smart Citations

Pharmacological inhibition of CSF1R by GW2580 reduces microglial proliferation and is protective against neuroinflammation and dopaminergic neurodegeneration

et al. 2019

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“…Taking advantage of a newly available mitochondrially defective transgenic mouse model of Parkinson’s disease (PD), the MitoPark mouse, this group corroborates gene environment interactions associated with mitochondrial defects in the nigral dopaminergic system (Langley et al, 2018). Loss of ATP13A2 function in ATP13A2-deficient mice is also shown as a risk factor for increased sensitivity to Mn in vivo (Fleming et al, 2018). Harischandra et al addressed the role of Mn in modulating extracellular miRNA content through exosomal release from dopaminergic neurons, establishing that Mn treatment in α-synuclein-expressing cells increases the protein Rab27a, the latter regulating exosome release from cells (Harischandra et al, 2018).…”

Section: Scientific Advances Reported At the Conferencementioning

confidence: 99%

Neurotoxicity of manganese: Indications for future research and public health intervention from the Manganese 2016 conference

et al. 2018

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Manganese is an essential trace element, but also at high levels a neurotoxicant. Manganese neurotoxicity has been extensively studied since its discovery in highly exposed workers. The International conference MANGANESE 2016 held at the Icahn School of Medicine at Mount Sinai in New York provided relevant updates on manganese research in relation to both occupational and environmental exposures. Epidemiological, toxicological and cellular studies reported at the conference have yielded new insights on mechanisms of manganese toxicity and on opportunities for preventive intervention. Strong evidence now exists for causal associations between manganese and both neurodevelopmental and neurodegenerative disorders. The neurodevelopmental effects of early life exposures are an example of the developmental origin of health and disease (DOHAD) concept. Brain imaging has rapidly become an important tool for examining brain areas impacted by manganese at various life stages. Candidate biomarkers of exposure are being identified in hair, nails, and teeth and reflect different exposure windows and relate to different health outcomes. Sex differences were reported in several studies, suggesting that women are more susceptible. New evidence indicates that the transporter genes SLC30A10 and SLC39A8 influence both manganese homeostasis and toxicity. New potential chelation modalities are being developed.

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Role of Astrocytes in Manganese Neurotoxicity Revisited

Sidoryk‐Węgrzynowicz

Pajarillo

et al. 2019

Neurochem Res

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The effect of manganese exposure in Atp13a2-deficient mice

Cited by 22 publications

References 68 publications

Pharmacological inhibition of CSF1R by GW2580 reduces microglial proliferation and is protective against neuroinflammation and dopaminergic neurodegeneration

Pharmacological inhibition of CSF1R by GW2580 reduces microglial proliferation and is protective against neuroinflammation and dopaminergic neurodegeneration

Neurotoxicity of manganese: Indications for future research and public health intervention from the Manganese 2016 conference

Role of Astrocytes in Manganese Neurotoxicity Revisited

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