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Tytuł pozycji:

Regulation of brain iron uptake by apo- and holo-transferrin is dependent on sex and delivery protein

Tytuł:
Regulation of brain iron uptake by apo- and holo-transferrin is dependent on sex and delivery protein
Autorzy:
Stephanie L. Baringer
Elizabeth B. Neely
Kondaiah Palsa
Ian A. Simpson
James R. Connor
Temat:
Blood–brain barrier
Iron
H-ferritin
Transferrin
Sex difference
Neurology. Diseases of the nervous system
RC346-429
Źródło:
Fluids and Barriers of the CNS, Vol 19, Iss 1, Pp 1-10 (2022)
Wydawca:
BMC, 2022.
Rok publikacji:
2022
Kolekcja:
LCC:Neurology. Diseases of the nervous system
Typ dokumentu:
article
Opis pliku:
electronic resource
Język:
English
ISSN:
2045-8118
Relacje:
https://doaj.org/toc/2045-8118
DOI:
10.1186/s12987-022-00345-9
Dostęp URL:
https://doaj.org/article/f0ff6eb5fcb84770986126f54fddb6a5  Link otwiera się w nowym oknie
Numer akcesji:
edsdoj.f0ff6eb5fcb84770986126f54fddb6a5
Czasopismo naukowe
Abstract Background The brain requires iron for a number of processes, including energy production. Inadequate or excessive amounts of iron can be detrimental and lead to a number of neurological disorders. As such, regulation of brain iron uptake is required for proper functioning. Understanding both the movement of iron into the brain and how this process is regulated is crucial to both address dysfunctions with brain iron uptake in disease and successfully use the transferrin receptor uptake system for drug delivery. Methods Using in vivo steady state infusions of apo- and holo-transferrin into the lateral ventricle, we demonstrate the regulatory effects of brain apo- and holo-transferrin ratios on the delivery of radioactive 55Fe bound to transferrin or H-ferritin in male and female mice. In discovering sex differences in the response to apo- and holo-transferrin infusions, ovariectomies were performed on female mice to interrogate the influence of circulating estrogen on regulation of iron uptake. Results Our model reveals that apo- and holo-transferrin significantly regulate iron uptake into the microvasculature and subsequent release into the brain parenchyma and their ability to regulate iron uptake is significantly influenced by both sex and type of iron delivery protein. Furthermore, we show that cells of the microvasculature act as reservoirs of iron and release the iron in response to cues from the interstitial fluid of the brain. Conclusions These findings extend our previous work to demonstrate that the regulation of brain iron uptake is influenced by both the mode in which iron is delivered and sex. These findings further emphasize the role of the microvasculature in regulating brain iron uptake and the importance of cues regarding iron status in the extracellular fluid.
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