Environmentally relevant manganese overexposure alters neural cell morphology and differentiation in vitro

Parsons-White, Amy; Spitzer, Nadja

doi:10.1016/j.tiv.2018.02.015

Cited by 18 publications

(4 citation statements)

References 49 publications

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“…Environmentally relevant Mn exposure (500–800 μM for 24 h) is known to induce cytoskeletal reorganization in neurons with inhibition of neuronal differentiation and neurite outgrowth [ 72 ].…”

Section: Mn-induced Alterations In Subcellular and Multicellular Biologymentioning

confidence: 99%

Molecular Targets of Manganese-Induced Neurotoxicity: A Five-Year Update

Tinkov

Paoliello

Mazilina

et al. 2021

IJMS

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Understanding of the immediate mechanisms of Mn-induced neurotoxicity is rapidly evolving. We seek to provide a summary of recent findings in the field, with an emphasis to clarify existing gaps and future research directions. We provide, here, a brief review of pertinent discoveries related to Mn-induced neurotoxicity research from the last five years. Significant progress was achieved in understanding the role of Mn transporters, such as SLC39A14, SLC39A8, and SLC30A10, in the regulation of systemic and brain manganese handling. Genetic analysis identified multiple metabolic pathways that could be considered as Mn neurotoxicity targets, including oxidative stress, endoplasmic reticulum stress, apoptosis, neuroinflammation, cell signaling pathways, and interference with neurotransmitter metabolism, to name a few. Recent findings have also demonstrated the impact of Mn exposure on transcriptional regulation of these pathways. There is a significant role of autophagy as a protective mechanism against cytotoxic Mn neurotoxicity, yet also a role for Mn to induce autophagic flux itself and autophagic dysfunction under conditions of decreased Mn bioavailability. This ambivalent role may be at the crossroad of mitochondrial dysfunction, endoplasmic reticulum stress, and apoptosis. Yet very recent evidence suggests Mn can have toxic impacts below the no observed adverse effect of Mn-induced mitochondrial dysfunction. The impact of Mn exposure on supramolecular complexes SNARE and NLRP3 inflammasome greatly contributes to Mn-induced synaptic dysfunction and neuroinflammation, respectively. The aforementioned effects might be at least partially mediated by the impact of Mn on α-synuclein accumulation. In addition to Mn-induced synaptic dysfunction, impaired neurotransmission is shown to be mediated by the effects of Mn on neurotransmitter systems and their complex interplay. Although multiple novel mechanisms have been highlighted, additional studies are required to identify the critical targets of Mn-induced neurotoxicity.

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Section: Mn-induced Alterations In Subcellular and Multicellular Biologymentioning

confidence: 99%

Molecular Targets of Manganese-Induced Neurotoxicity: A Five-Year Update

Tinkov

Paoliello

Mazilina

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…The distortion of the spherical nanoparticles observed in samples analyzed after cell culture ( Fig. 9 ) could be due to interactions with physiological saline and medium required for mammalian cell culture [ 51 , 71 , 72 ].…”

Section: Resultsmentioning

confidence: 99%

Biocompatible antibiotic-coupled nickel-titanium nanoparticles as a potential coating material for biomedical devices

McGlumphy,

Damai,

Salameh

et al. 2024

Heliyon

Self Cite

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“…It has, therefore, been suggested that NSCs are capable of compensating for lost or damaged cells in the injured brain, and NSC transplantation has been tested as a potential treatment for many types of neurological damage, including ischemia and traumatic brain injury, neurodegenerative disorders [40], as well as lead exposure [41]. Importantly, neurogenesis has been shown to be impaired in animal models of Mn exposure [30] ; it slows the proliferation of NSCs in vivo and in vitro [42,43]. The hippocampal region of the developing brain is especially vulnerable to Mn-induced neurotoxicity and the subsequent spatial learning and cognitive impairments [34]; this, coupled with the recent observations that impaired neurogenesis in animals exposed to Mn during development closely resembles the structural disruptions common to some neurodegenerative diseases [4], prompted us to investigate if these functional deficits could be restored by NSC transplantation in young Mnexposed mice.…”

Section: Discussionmentioning

confidence: 99%

Intracerebral Transplantation of Neural Stem Cells Restores Manganese-Induced Cognitive Deficits in Mice

et al. 2021

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Manganese (Mn) is a potent neurotoxin known to cause long-lasting structural damage and progressive cognitive deficits in the brain. However, new therapeutic approaches are urgently needed since current treatments only target symptoms of Mn exposure. Recent studies have suggested a potential role for multipotent neural stem cells (NSCs) in the etiology of Mn-induced cognitive deficits. In this study, we evaluated the effect of direct intracerebral transplantation of NSCs on cognitive function of mice chronically exposed to MnCl2, and further explored the distribution of transplanted NSCs in brain tissues. NSCs were isolated and bilaterally injected into the hippocampal regions or lateral ventricles of Mn-exposed mice. The results showed that many transplanted cells migrated far away from the injection sites and survived in vivo in the Mn-exposed mouse brain, implying enhanced neurogenesis in the host brain. We found that NSCs transplanted into either the hippocampal regions or the lateral ventricles significantly improved spatial learning and memory function of the Mn-exposed mice in the Morris water maze. Immunofluorescence analyses indicated that some surviving NSCs differentiated into neurons or glial cells, which may have become functionally integrated into the impaired local circuits, providing a possible cellular basis for the improvement of cognitive function in NSC-transplanted mice. Taken together, our findings confirm the Mn-induced impairment of neurogenesis in the brain and underscore the potential of treating Mn exposure by NSC transplantation, providing a practical therapeutic strategy against this type of neurotoxicity.

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Environmentally relevant manganese overexposure alters neural cell morphology and differentiation in vitro

Cited by 18 publications

References 49 publications

Molecular Targets of Manganese-Induced Neurotoxicity: A Five-Year Update

Molecular Targets of Manganese-Induced Neurotoxicity: A Five-Year Update

Biocompatible antibiotic-coupled nickel-titanium nanoparticles as a potential coating material for biomedical devices

Intracerebral Transplantation of Neural Stem Cells Restores Manganese-Induced Cognitive Deficits in Mice

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