Methylcyclopentadienyl Manganese Tricarbonyl Alter Behavior and Cause Ultrastructural Changes in the Substantia Nigra of Rats: Comparison with Inorganic Manganese Chloride

Zhu, Qi-Feng; Lü, Lili; Fang, Yuanyuan; Wu, Jie; Huang, Zhao-Ying; Zheng, Xiao-Wei; Song, Han-Xiao; Aschner, Michael; Song, Ce; Jiang, Yue-Ming

doi:10.1007/s11064-022-03606-z

Cited by 7 publications

(4 citation statements)

References 55 publications

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“…34 In animal studies, Mn and Fe have been shown to cause a series of neurological diseases, characterized by cognitive and behavioural disorders and attention deficits. 35,36 And in vitro studies, excessive Mn exposure can cause apoptosis in PC12 cells, while excessive Fe levels can trigger oxidative stress and promote cell death. 37,38 Body weight is an important index for evaluating the growth and development of rats, reflecting their overall health in response to toxicants.…”

Section: Discussionmentioning

confidence: 99%

“…Continuous Fe exposure can also cause Parkinson's disease‐like symptoms, including learning and memory dysfunction 34 . In animal studies, Mn and Fe have been shown to cause a series of neurological diseases, characterized by cognitive and behavioural disorders and attention deficits 35,36 . And in vitro studies, excessive Mn exposure can cause apoptosis in PC12 cells, while excessive Fe levels can trigger oxidative stress and promote cell death 37,38 …”

Section: Discussionmentioning

confidence: 99%

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Sodium para‐aminosalicylic acid attenuates combined manganese/iron‐induced cortical synaptic damage in rats

Song,

Xie,

Fang

et al. 2024

Basic Clin Pharma Tox

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We established experimental models of manganese (Mn) and iron (Fe) exposure in vitro and in vivo, and addressed the effects of manganese and iron combined exposure on the synaptic function of pheochromocytoma derived cell line 12 (PC12) cells and rat cortex, respectively. We investigated the protective effect of sodium para‐aminosalicylate (PAS‐Na) on manganese and iron combined neurotoxicity, providing a scientific basis for the prevention and treatment of ferromanganese combined neurotoxicity. Western blot and reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR) were performed to detect the expression levels of protein and mRNA related to synaptic damage. Y‐maze novelty test and balance beam test were used to evaluate the motor and cognitive function of rats. Haematoxylin and eosin (H&E) and Nissl staining were performed to observe the cortical damage of rats. The results showed that the combined exposure of Mn and Fe in rats led to a synergistic effect, attenuating growth and development, and altering learning and memory as well as motor function. The combination of Mn and Fe also caused damage to the synaptic structure of PC12 cells, which is manifested as swelling of dendrites and axon terminals, and even lead to cell death. PAS‐Na displayed some antagonistic effects against the Mn‐ and Fe‐induced synaptic structural damage, growth, learning and memory impairment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Sodium para‐aminosalicylic acid attenuates combined manganese/iron‐induced cortical synaptic damage in rats

Song,

Xie,

Fang

et al. 2024

Basic Clin Pharma Tox

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“…Rats were housed under controlled conditions (22 ± 2°C, 455 ± 10% relative humidity, 12 hr light/ dark cycle) with free food and water access. Rat treatments were implemented as in a prior study (Zhu et al, 2022). Briefly, following a 1-week acclimation period, 18 total rats (220 ± 20 g, 8 weeks old; 9 males, 9 females) were randomly assigned to three groups (n = 3/group/ sex): control, MMT, and positive control (MnCl 2 ) groups.…”

Section: Animal Treatmentsmentioning

confidence: 99%

“…Environmental sources of Mn exposure include airborne Mn derived from the gasoline antiknock additive Methylcyclopentadienyl Manganese Tricarbonyl (MMT), the utilization of permanganate to purify drinking water, and occupational exposure to agrochemicals, including Maneb and Mancozeb (Röllin and Nogueira, 2011). Exposure to MMT or MnCl 2 can promote the development of cognitive and motor deficits in both female and male rats, resulting in slower weight gain, reductions in TH expression, pronounced pathological damage to SNpc (substantia nigra pars compacta) neurons, and higher levels of Iba1 microglial activation (Zhu et al, 2022). These findings are similar to those observed in cases of atypical Parkinsonism.…”

Section: Introductionmentioning

confidence: 99%

Small noncoding RNA dysregulation is implicated in manganism in a rat model of methylcyclopentadienyl manganese tricarbonyl-induced unrepaired striatum damage

Zhu,

Jiang,

Song

et al. 2023

J. Toxicol. Sci.

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The accumulation of excessively high manganese levels within the brain can contribute to a series of Parkinsonian symptoms referred to as manganism. The gasoline antiknock additive Methylcyclopentadienyl Manganese Tricarbonyl (MMT) is an environmental source of manganese exposure and can induce manganism in rats. While some prior reports have demonstrated the differential expression of small noncoding RNAs (sncRNAs) in patients with Parkinson's disease (PD), the degree of sncRNA dysfunction in manganism has yet to be clearly documented. As sncRNAs such as transfer RNA-derived small RNAs (tsRNAs) and ribosomal RNA-derived small RNAs (rsRNAs) exhibit high levels of modifications such as 3' terminal 3'-phosphate and 2',3'-cyclic phosphate modifications that disrupt the process of adapter ligation and m 1 A, m 3 C, m 1 G, and m 2 2 G RNA methylation, these transcripts are not detected in traditional small RNA-sequencing studies. Here, differential sncRNA expression was analyzed by comparing a rat model of MMT-induced unrepaired striatum damage to appropriate control samples via PANDORA-Seq, which can detect highly modified sncRNAs. Following the removal of sncRNA modifications, this approach identified 599 sncRNAs that were differentially expressed in the striatum of MMTexposed rats relative to controls, as well as 1155 sncRNAs that were differentially expressed in Mn-treated and control rats. Additional functional analyses were performed to predict the putative targets of these sncRNAs, implicating a role for such sncRNA dysregulation in the pathogenesis of manganism in this rat model system.

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Signal Transduction Associated with Mn-induced Neurological Dysfunction

Zheng,

Fang,

Lin

et al. 2023

Biol Trace Elem Res

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Methylcyclopentadienyl Manganese Tricarbonyl Alter Behavior and Cause Ultrastructural Changes in the Substantia Nigra of Rats: Comparison with Inorganic Manganese Chloride

Cited by 7 publications

References 55 publications

Sodium para‐aminosalicylic acid attenuates combined manganese/iron‐induced cortical synaptic damage in rats

Sodium para‐aminosalicylic acid attenuates combined manganese/iron‐induced cortical synaptic damage in rats

Small noncoding RNA dysregulation is implicated in manganism in a rat model of methylcyclopentadienyl manganese tricarbonyl-induced unrepaired striatum damage

Signal Transduction Associated with Mn-induced Neurological Dysfunction

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