H‐ferritin expression in astrocytes is necessary for proper oligodendrocyte development and myelination

Cheli, Verónica T.; González, Diara A. Santiago; Wan, Qiuchen; Denaroso, Giancarlo; Wan, Rensheng; Rosenblum, Shaina L.; Paez, Pablo M.

doi:10.1002/glia.24083

Cited by 24 publications

(22 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Microglia also express TfR1 and reduce iron toxicity by promoting the influx of excess iron (for storage in ferritin) via the TfR1/DMT1 pathway ( Qian and Ke, 2019 ). Microglia and astrocytes are capable of releasing ferritin carrying Fe 3+ to supplement the iron deficiency or to support oligodendrocytes for myelination or remyelination ( Cheli et al, 2021 ). Iron is essential for myelination in oligodendrocytes, which are the most iron-rich cell type in the brain.…”

Section: Iron Metabolism In Healthy and Alzheimer’s Disease Brainmentioning

confidence: 99%

Iron Dyshomeostasis and Ferroptosis: A New Alzheimer’s Disease Hypothesis?

Wang

Shen

et al. 2022

Front. Aging Neurosci.

View full text Add to dashboard Cite

Iron plays a crucial role in many physiological processes of the human body, but iron is continuously deposited in the brain as we age. Early studies found iron overload is directly proportional to cognitive decline in Alzheimer’s disease (AD). Amyloid precursor protein (APP) and tau protein, both of which are related to the AD pathogenesis, are associated with brain iron metabolism. A variety of iron metabolism-related proteins have been found to be abnormally expressed in the brains of AD patients and mouse models, resulting in iron deposition and promoting AD progression. Amyloid β (Aβ) and hyperphosphorylated tau, two pathological hallmarks of AD, can also promote iron deposition in the brain, forming a vicious cycle of AD development-iron deposition. Iron deposition and the subsequent ferroptosis has been found to be a potential mechanism underlying neuronal loss in many neurodegenerative diseases. Iron chelators, antioxidants and hepcidin were found useful for treating AD, which represents an important direction for AD treatment research and drug development in the future. The review explored the deep connection between iron dysregulation and AD pathogenesis, discussed the potential of new hypothesis related to iron dyshomeostasis and ferroptosis, and summarized the therapeutics capable of targeting iron, with the expectation to draw more attention of iron dysregulation and corresponding drug development.

show abstract

Section: Iron Metabolism In Healthy and Alzheimer’s Disease Brainmentioning

confidence: 99%

Iron Dyshomeostasis and Ferroptosis: A New Alzheimer’s Disease Hypothesis?

Wang

Shen

et al. 2022

Front. Aging Neurosci.

View full text Add to dashboard Cite

show abstract

“…Iron deficiency leads to learning and memory impairment (Lozoff et al, 2006), while its excess is associated with aging and neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease and multiple sclerosis (Belaidi & Bush, 2016; Liu et al, 2019; Molina‐Holgado et al, 2007; Moller et al, 2019; Stephenson et al, 2014; Zecca et al, 2004). Iron is also essential to oligodendrocyte differentiation and functions (Cheli et al, 2020; Cheli et al, 2021; Stephenson et al, 2014). Emerging evidence indicates that brain iron overload occurs in case of systemic iron overload or hemochromatosis (HH) and affects brain functions.…”

Section: Introductionmentioning

confidence: 99%

“…Astrocytes, an important glial cell type, are thought to be crucial actors in this matter (Cheli et al, 2020; Cheli et al, 2021; Dringen et al, 2007; Hohnholt & Dringen, 2013). Astrocytes are highly polarized cells interfacing neurons and the blood vessels.…”

Section: Introductionmentioning

confidence: 99%

Physiopathological changes of ferritinmRNAdensity and distribution in hippocampal astrocytes in the mouse brain

Tortuyaux

Avila-Gutierrez

Oudart

et al. 2023

Journal of Neurochemistry

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 is 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: aging, the hepcidin knock‐out mouse model of hemochromatosis and the APP/PS1dE9 mouse model of Alzheimer's 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. Aging and absence of hepcidin caused an increased Fth1/Ftl1 ratio in astrocytes and in the case of aging, led to a redistribution of Fth1 mRNAs in astrocytic fine processes. In contrast, in AD mice, we observed a lower Fth1/Ftl1 ratio. Fth1 mRNAs became more somatic and Ftl1 mRNAs redistributed in large processes of astrocytes proximal to Amyloid beta (Aß) deposits. Hence, we propose that regulation of ferritin mRNA density and distribution in astrocytes contribute to iron homeostasis in physiology and pathophysiology.

show abstract

“…Iron deficiency leads to learning and memory impairment (Lozoff et al, 2006), while its excess is associated with ageing and neurodegenerative disorders including Alzheimer’s disease (AD), Parkinson’s disease and multiple sclerosis (Belaidi & Bush, 2016; Liu, Liang, & Soong, 2019; Molina-Holgado, Hider, Gaeta, Williams, & Francis, 2007; Stephenson, Nathoo, Mahjoub, Dunn, & Yong, 2014; Zecca, Youdim, Riederer, Connor, & Crichton, 2004). Iron is also essential to oligodendrocyte differentiation and functions (Cheli, Correale, Paez, & Pasquini, 2020; Cheli et al, 2021; Stephenson et al, 2014). Thus, understanding how brain cells regulate iron levels is critical and the molecular mechanisms behind these regulations are potential therapeutic targets to control iron imbalance in the brain.…”

Section: Introductionmentioning

confidence: 99%

“…Astrocytes, an important glial cell type, are thought to be crucial actors in this matter (Cheli et al, 2020; Cheli et al, 2021; Dringen, Bishop, Koeppe, Dang, & Robinson, 2007; Hohnholt & Dringen, 2013). Astrocytes are highly polarized cells interfacing neurons and the blood vessels.…”

Section: Introductionmentioning

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

H‐ferritin expression in astrocytes is necessary for proper oligodendrocyte development and myelination

Cited by 24 publications

References 59 publications

Iron Dyshomeostasis and Ferroptosis: A New Alzheimer’s Disease Hypothesis?

Iron Dyshomeostasis and Ferroptosis: A New Alzheimer’s Disease Hypothesis?

Physiopathological changes of ferritinmRNAdensity and distribution in hippocampal astrocytes in the mouse brain

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

Contact Info

Product

Resources

About