The aging brain: impact of heavy metal neurotoxicity

Ijomone, Omamuyovwi M.; Ifenatuoha, Chibuzor W.; Aluko, Oritoke Modupe; Ijomone, Olayemi K.; Aschner, Michael

doi:10.1080/10408444.2020.1838441

Cited by 60 publications

(35 citation statements)

References 152 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The aim of the present study was to determine the adverse neurological effects induced by PM 2.5 constituents, which showed that the contents of several metallic elements, including Cu, Zn, Ni, Mn, Sn, V, Rb, Pb, Al, Be, Cs, Co, Th, and U, were significantly associated with NfL. The neurotoxicity of these metals has been examined in previous epidemiological and toxicological studies. − For example, an in vitro study showed that Ni exposure induces oxidative stress-associated neuronal damage . Co exposure exhibited a dose- and time-dependent toxicities in neurons and astrocytes, with neurons presenting particular sensitivity .…”

Section: Discussionmentioning

confidence: 93%

Associations of Short-Term Exposure to Fine Particulate Matter with Neural Damage Biomarkers: A Panel Study of Healthy Retired Adults

Song

Sun

et al. 2021

Environ. Sci. Technol.

View full text Add to dashboard Cite

Exposure to fine particulate matter (PM 2.5 ) is associated with various adverse health effects, such as respiratory and cardiovascular diseases. This study aimed to evaluate the association of PM 2.5 with neural damage biomarkers. A total of 34 healthy retirees were recruited from Xinxiang Medical University from December 2018 to April 2019. Concentrations of PM 2.5 constituents including 24 metals and nonmetallic elements and 6 ions, and 5 biomarkers of neural damage including brainderived neurotrophic factor (BDNF), neurofilament light chain (NfL), neuronspecific enolase (NSE), protein gene product 9.5 (PGP9.5), and S100 calciumbinding protein B (S100B) in serum were measured. A linear mixed-effect model was employed to estimate the association of PM 2.5 and its constituents with neural damage biomarkers. Modification effects of glutathione S-transferase theta 1 gene (GSTT1) polymorphism, sex, education, and physical activity on PM 2.5 exposure with neural damage were explored. PM 2.5 and its key constituents were significantly associated with neural damage biomarkers. A 10 μg/m 3 increase in PM 2.5 concentration was associated with 2.

show abstract

Section: Discussionmentioning

confidence: 93%

Associations of Short-Term Exposure to Fine Particulate Matter with Neural Damage Biomarkers: A Panel Study of Healthy Retired Adults

Song

Sun

et al. 2021

Environ. Sci. Technol.

View full text Add to dashboard Cite

show abstract

“…On the other hand, the central nervous system is well protected against copper for a long time by the blood brain barrier. Nevertheless, it is highly vulnerable to heavy metal intoxication [ 37 ].…”

Section: Discussion 1 Previous Reports On Homozygous Wd Twins In the ...mentioning

confidence: 99%

Different Response Behavior to Therapeutic Approaches in Homozygotic Wilson’s Disease Twins with Clinical Phenotypic Variability: Case Report and Literature Review

Samadzadeh

Kruschel

Novak

et al. 2022

Genes

View full text Add to dashboard Cite

Background: Wilson’s disease (WD) is an autosomal-recessive disorder of copper deposition caused by pathogenic variants in the copper-transporting ATP7B gene. There is not a clear correlation between genotype and phenotype in WD regarding symptom manifestations. This is supported by the presentation of genetically identical WD twins with phenotypic discordance and different response behavior to WD-specific therapy. Case Presentation: One of the female homozygous twins (age: 26 yrs) developed writing, speaking, swallowing and walking deficits which led to in-patient examination without conclusive results but recommended genetic testing. Both sisters were tested and were heterozygous for the C.2304dupC;p(Met769Hisf*26) and the C.3207C>A;p(His1069Gln) mutation. Self-medication of the affected sibling with 450 mg D-penicillamine (DPA) did not prevent further deterioration. She developed a juvenile parkinsonian syndrome and became wheelchair-bound and anarthric. A percutaneous endoscopic gastrostomy was applied. Her asymptomatic sister helped her with her daily life. Despite the immediate increase of the DPA dose (up to 1800 mg within 3 weeks) in the severely affected patient and the initiation of DPA therapy (up to 600 mg within 2 weeks) in the asymptomatic patient after the first visit in our institution, liver function tests further deteriorated in both patients. After 2 months, the parkinsonian patient started to improve and walk again, but experienced several falls, broke her right shoulder and underwent two necessary surgical interventions. With further consequent copper elimination therapy, liver dysfunction improved in both patients, without need for orthotopic liver transplantation (LTX) in the severely affected patient. Her excellent recovery of liver and brain dysfunction was only transiently interrupted by the development of a nephrotic syndrome which disappeared after switching to Cuprior®. Unfortunately, she died from fulminant pneumonia. Conclusion: Despite identical genetic disposition, WD symptom presentations may develop differently in monozygotic twins, and they may need to be placed on a very different therapeutical regimen. The underlying gene-environment interaction is unclear so far.

show abstract

“…Iron accumulates in the brain of healthy subjects with age (Ijomone, Ifenatuoha, Aluko, Ijomone, & Aschner, 2020). Here, we performed FISH experiments on 10-month-old WT mice and compared the 10 level and distribution of ferritin mRNAs between 6-and 10-month-old WT hippocampal astrocytes (Fig.…”

Section: Ageing Increases the Fth1/ftl1 Ratio In Hippocampal Astrocyt...mentioning

confidence: 99%

Physiopathological changes of ferritin mRNA density and distribution in hippocampal astrocytes in the mouse brain

Tortuyaux

Oudart

Mazaré

et al. 2022

Preprint

View full text Add to dashboard Cite

Astrocytes are thought to play a crucial role in brain iron homeostasis. How they accomplish this regulation in vivo remains unclear. In a recent transcriptomic analysis, we showed that polysomal Ftl1 and Fth1 mRNAs, encoding the ferritin light (Ftl) and heavy (Fth) chains that assemble into ferritin, a critical complex for iron storage and reduction, are enriched in perisynaptic astrocytic processes as compared to astrocytic soma. These data suggested that ferritin translation plays a specific role at the perisynaptic astrocytic interface and is tighly regulated by local translation. Here, we used our recently described AstroDot 3D in situ methodology to study the density and localization of ferritin mRNAs in astrocytes in the hippocampus in three different contexts in which local or systemic iron overload has been documented: ageing, the hepcidin knock-out mouse model of hemochromatosis and the APP/PS1dE9 mouse model of Alzheimers disease (AD). Our results showed that in wild type mice, Fth1 mRNA density was higher than Ftl1 and that both mRNAs were mostly distributed in astrocyte fine processes. Ageing and absence of hepcidin caused an increased Fth1/Ftl1 ratio in astrocytes and in the case of ageing, led to a redistribution of Fth1 mRNAs in astrocytic fine processes. In contrast, in AD mice, we observed a lower Fth1/Ftl1 ratio and Fth1 mRNAs became more somatic. Hence, we propose that regulation of ferritin mRNA density and distribution in astrocytes regulates iron homeostasis in physiology and pathophysiology.

show abstract

The aging brain: impact of heavy metal neurotoxicity

Cited by 60 publications

References 152 publications

Associations of Short-Term Exposure to Fine Particulate Matter with Neural Damage Biomarkers: A Panel Study of Healthy Retired Adults

Associations of Short-Term Exposure to Fine Particulate Matter with Neural Damage Biomarkers: A Panel Study of Healthy Retired Adults

Different Response Behavior to Therapeutic Approaches in Homozygotic Wilson’s Disease Twins with Clinical Phenotypic Variability: Case Report and Literature Review

Physiopathological changes of ferritin mRNA density and distribution in hippocampal astrocytes in the mouse brain

Contact Info

Product

Resources

About