Trace elements profile in the blood of Huntington’ disease patients

Squadrone, Stefania; Brizio, Paola; Abete, Maria Cesarina; Brusco, Alfredo

doi:10.1016/j.jtemb.2019.09.006

Cited by 27 publications

(12 citation statements)

References 17 publications

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“…However, some previous studies also used blood as a biological sample to assess the status of some essential trace elements in the human body ( 32 , 33 ). Moreover, as a microenvironment composed of a serum ultrafiltrate, follicular fluid is in direct contact with a developing oocyte and its surrounding somatic cells ( 34 , 35 ). Compared with blood, follicular fluid better reflects the internal environmental state ( 36 ).…”

Section: Discussionmentioning

confidence: 99%

The association between essential trace element (copper, zinc, selenium, and cobalt) status and the risk of early embryonic arrest among women undergoing assisted reproductive techniques

Cao¹,

Liang²,

Shen³

et al. 2022

Front. Endocrinol.

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BackgroundEarly embryonic arrest (EEA) leads to repeated cessation of fresh cycles among infertile women undergoing in vitro fertilization (IVF). Whether the levels of some essential trace elements [copper (Cu), zinc (Zn), selenium (Se) and cobalt (Co)] in the bodies of women are related to the risk of EEA warrants study.ObjectiveOur study aimed to investigate the associations of peripheral blood levels of Cu, Zn, Se, and Co and their mixtures with the risk of EEA.MethodsA total of 74 EEA cases (123 IVF cycles) and 157 controls (180 IVF cycles) from the reproductive center of the First Affiliated Hospital of Anhui Medical University in Hefei, China, between June 2017 and March 2020 were included in our study. Demographic and clinical data were collected from electronic medical records. Cu, Zn, Se, and Co levels were measured in blood samples collected on the day of oocyte retrieval when infertile women entered clinical treatment for the first time using an inductively coupled plasma mass spectrometer (ICP−MS). Generalized estimating equation (GEE) models were used to evaluate the associations of four essential trace element concentrations individually with the risk of EEA, and Bayesian kernel machine regression (BKMR) was used to explore the associations between four essential trace element mixtures and the risk of EEA.ResultsSe concentrations of infertile women were significantly lower in the case group compared with the control group. Co levels were significantly higher in the case group compared with the control group. The differences in Cu and Zn concentrations between the two groups were not significant. Based on single-metal models, Co was positively associated with the risk of EEA before and after adjustment for all confounders (odd ratio (OR) = 1.72, 95% confidence interval (CI): 1.18−2.52; OR = 2.27, 95% CI: 1.37−3.77, respectively), and Se was negatively associated with the risk of EEA before adjustment for all confounders (OR = 0.18, 95% CI: 0.07−0.51). BKMR analyses showed that Se was significantly and negatively associated with the risk of EEA when all the other three metals (Cu, Zn, and Co) were fixed at the 25th, 50th, or 75th percentiles, whereas Zn displayed a significant and positive association with the risk of EEA when all the other three metals (Cu, Se and Co) were fixed at the 25th, 50th, or 75th percentiles. Co did not show any effect on the risk of EEA when all the other metals (Cu, Zn, and Se) were fixed at the 25th, 50th, or 75th percentiles. In addition, an increasing trend of the joint effect of four essential trace elements on the risk of EEA was found, although it was not statistically significant.ConclusionThe levels of essential trace elements (Cu, Zn, Se, and Co) might correlate with the risk of EEA to some extent. The present study might provide a real-world perspective on the relationship between essential trace elements and the risk of EEA when considering them as a single element or as mixtures.

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Section: Discussionmentioning

confidence: 99%

The association between essential trace element (copper, zinc, selenium, and cobalt) status and the risk of early embryonic arrest among women undergoing assisted reproductive techniques

Cao¹,

Liang²,

Shen³

et al. 2022

Front. Endocrinol.

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“…The analyses of brain autopsy from HD patients indicate a significant reduction of Se, an essential metal with protective properties against cytotoxicity and redox imbalance (Lu et al, 2014). Alternatively, a recent study reports that Se, iron, and chromium are among the essential elements that are considerably elevated in the blood samples of HD patients compared to normal individuals (Squadrone et al, 2020). In Caenorhabditis elegans, treatment with low doses of Se NPs reverses brain condition by improving oxidative status and inhibiting the aggregation of huntingtin proteins, suggesting the potential of the compound in the treatment of HD (Cong et al, 2019).…”

Section: Huntington Disease (Hd)mentioning

confidence: 99%

The Application of Nanotechnology for the Diagnosis and Treatment of Brain Diseases and Disorders

Ngowi

Wang

Qian

et al. 2021

Front. Bioeng. Biotechnol.

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Brain is by far the most complex organ in the body. It is involved in the regulation of cognitive, behavioral, and emotional activities. The organ is also a target for many diseases and disorders ranging from injuries to cancers and neurodegenerative diseases. Brain diseases are the main causes of disability and one of the leading causes of deaths. Several drugs that have shown potential in improving brain structure and functioning in animal models face many challenges including the delivery, specificity, and toxicity. For many years, researchers have been facing challenge of developing drugs that can cross the physical (blood–brain barrier), electrical, and chemical barriers of the brain and target the desired region with few adverse events. In recent years, nanotechnology emerged as an important technique for modifying and manipulating different objects at the molecular level to obtain desired features. The technique has proven to be useful in diagnosis as well as treatments of brain diseases and disorders by facilitating the delivery of drugs and improving their efficacy. As the subject is still hot, and new research findings are emerging, it is clear that nanotechnology could upgrade health care systems by providing easy and highly efficient diagnostic and treatment methods. In this review, we will focus on the application of nanotechnology in the diagnosis and treatment of brain diseases and disorders by illuminating the potential of nanoparticles.

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“…Altered homeostasis of essential elements such as iron, chromium and selenium has been observed in the HD patients [32,33] and mice model [34]. Specially, increased level of zinc is detected in the blood of HD patients, indicating that mutant Htt (mHtt) might impair zinc homeostasis [32]. Nevertheless, it remains unclear whether mHtt affect zinc homeostasis in the brain.…”

Section: Introductionmentioning

confidence: 99%

Disruption of zinc transporter ZnT3 transcriptional activity and synaptic vesicular zinc in the brain of Huntington’s disease transgenic mouse

Niu

Yang

Wang

et al. 2022

Preprint

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Background: Huntington’s disease (HD) is a neurodegenerative disease that involves a complex combination of psychiatric, cognitive and motor impairments. Synaptic dysfunction has been implicated in HD pathogenesis. However, the mechanisms have not been clearly delineated. Synaptic vesicular zinc is closely linked to modulating synaptic transmission and maintaining cognitive ability. It is signifcant to assess zinc homeostasis for further revealing the pathogenesis of synaptic dysfunction and cognitive impairment in HD. Results: Histochemical staining by autometallography indicated that synaptic vesicular zinc was decreased in the hippocampus, cortex and striatum of N171-82Q HD transgenic mice. Analyses by immunohistochemistry, Western blot and RT-PCR found that the expression of zinc transporter 3 (ZnT3) required for transport of zinc into synaptic vesicles was obviously reduced in these three brain regions of the HD mice aged from 14 to 20 weeks and BHK cells expressing mutant huntingtin. Signifcantly, dual-luciferase reporter gene and chromatin immunoprecipitation assays demonstrated that transcription factor Sp1 could activate ZnT3 transcription via its binding to the GC boxes in ZnT3 promoter. Moreover, mutant huntingtin was found to inhibit the binding of Sp1 to the promoter of ZnT3 and down-regulate ZnT3 expression, and the decline in ZnT3 expression could be ameliorated through overexpression of Sp1. Conclusions: This is frst study to reveal a signifcant loss of synaptic vesicular zinc and a decline in ZnT3 transcriptional activity in the HD transgenic mice. Our work sheds a novel mechanistic insight into pathogenesis of HD that mutant huntingtin down-regulates expression of ZnT3 through inhibiting binding of Sp1 to the promoter of ZnT3 gene, causing disruption of synaptic vesicular zinc homeostasis. Disrupted vesicular zinc ultimately leads to early synaptic dysfunction and cognitive defcits in HD. It is also suggested that maintaining normal synaptic vesicular zinc concentration is a potential therapeutic strategy for HD.

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Trace elements profile in the blood of Huntington’ disease patients

Cited by 27 publications

References 17 publications

The association between essential trace element (copper, zinc, selenium, and cobalt) status and the risk of early embryonic arrest among women undergoing assisted reproductive techniques

The association between essential trace element (copper, zinc, selenium, and cobalt) status and the risk of early embryonic arrest among women undergoing assisted reproductive techniques

The Application of Nanotechnology for the Diagnosis and Treatment of Brain Diseases and Disorders

Disruption of zinc transporter ZnT3 transcriptional activity and synaptic vesicular zinc in the brain of Huntington’s disease transgenic mouse

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