Iron accumulation in the choroid plexus, ependymal cells and CNS parenchyma in a rat strain with low-grade haemolysis of fragile macrocytic red blood cells.
cerebrospinal fluid
erythrocyte osmotic fragility
iron overload
kidney proximal tubule
multiple sclerosis
zitter rat
Journal
Brain pathology (Zurich, Switzerland)
ISSN: 1750-3639
Titre abrégé: Brain Pathol
Pays: Switzerland
ID NLM: 9216781
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
16
06
2020
revised:
16
10
2020
accepted:
18
11
2020
pubmed:
22
11
2020
medline:
21
12
2021
entrez:
21
11
2020
Statut:
ppublish
Résumé
Iron accumulation in the CNS is associated with many neurological diseases via amplification of inflammation and neurodegeneration. However, experimental studies on iron overload are challenging, since rodents hardly accumulate brain iron in contrast to humans. Here, we studied LEWzizi rats, which present with elevated CNS iron loads, aiming to characterise choroid plexus, ependymal, CSF and CNS parenchymal iron loads in conjunction with altered blood iron parameters and, thus, signifying non-classical entry sites for iron into the CNS. Non-haem iron in formalin-fixed paraffin-embedded tissue was detected via DAB-enhanced Turnbull Blue stainings. CSF iron levels were determined via atomic absorption spectroscopy. Ferroportin and aquaporin-1 expression was visualised using immunohistochemistry. The analysis of red blood cell indices and serum/plasma parameters was based on automated measurements; the fragility of red blood cells was manually determined by the osmotic challenge. Compared with wild-type animals, LEWzizi rats showed strongly increased iron accumulation in choroid plexus epithelial cells as well as in ependymal cells of the ventricle lining. Concurrently, red blood cell macrocytosis, low-grade haemolysis and significant haemoglobin liberation from red blood cells were apparent in the peripheral blood of LEWzizi rats. Interestingly, elevated iron accumulation was also evident in kidney proximal tubules, which share similarities with the blood-CSF barrier. Our data underscore the importance of iron gateways into the CNS other than the classical route across microvessels in the CNS parenchyma. Our findings of pronounced choroid plexus iron overload in conjunction with peripheral iron overload and increased RBC fragility in LEWzizi rats may be seminal for future studies of human diseases, in which similar constellations are found.
Identifiants
pubmed: 33220123
doi: 10.1111/bpa.12920
pmc: PMC8018038
doi:
Substances chimiques
Atrn protein, rat
0
Membrane Proteins
0
Iron
E1UOL152H7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
333-345Subventions
Organisme : Austrian Science Fund projects
ID : P27744-B27
Organisme : Austrian Science Fund projects
ID : P24245-B19
Organisme : Austrian Science Fund projects
ID : UE10207001
Organisme : Austrian Science Fund projects
ID : APW1205-B09
Informations de copyright
© 2020 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.
Références
Science. 1988 Sep 9;241(4871):1339-42
pubmed: 3413496
Arch Histol Cytol. 2007 Apr;70(1):1-19
pubmed: 17558140
FASEB J. 2005 Jan;19(1):76-8
pubmed: 15533949
Brain. 2011 Apr;134(Pt 4):959-68
pubmed: 21398376
Metab Brain Dis. 2009 Dec;24(4):673-84
pubmed: 19851851
J Neurochem. 1958 Oct;3(1):41-51
pubmed: 13611557
Cold Spring Harb Perspect Biol. 2017 Mar 1;9(3):
pubmed: 28003183
Nat Rev Immunol. 2013 Mar;13(3):206-18
pubmed: 23435332
JBR-BTR. 2013 Nov-Dec;96(6):391
pubmed: 24617189
Acta Psychiatr Neurol Scand Suppl. 1959;128:1-94
pubmed: 13636895
Neurochem Int. 1989;14(2):207-10
pubmed: 20504419
Fluids Barriers CNS. 2018 May 31;15(1):18
pubmed: 29848382
Tissue Barriers. 2014 Mar 19;2:e28426
pubmed: 25045600
J Trace Elem Med Biol. 2018 Sep;49:128-133
pubmed: 29895361
Methods Mol Biol. 2016;1304:211-29
pubmed: 25520281
Fluids Barriers CNS. 2016 Oct 31;13(1):19
pubmed: 27799072
Eur J Neurosci. 1995 Aug 1;7(8):1714-38
pubmed: 7582126
Acta Neuropathol Commun. 2019 Jan 31;7(1):14
pubmed: 30704526
Fluids Barriers CNS. 2018 Dec 12;15(1):34
pubmed: 30541599
Microsc Res Tech. 2001 Jan 1;52(1):5-20
pubmed: 11135444
J Comp Neurol. 1998 Aug 31;398(3):420-30
pubmed: 9714152
J Neurochem. 2004 Feb;88(4):813-20
pubmed: 14756801
Semin Pediatr Neurol. 2006 Sep;13(3):158-65
pubmed: 17101454
Nat Genet. 2001 Aug;28(4):345-9
pubmed: 11479594
Am J Clin Nutr. 1989 Oct;50(4):801-6
pubmed: 2801584
IUBMB Life. 2017 Jun;69(6):382-388
pubmed: 28150902
Glia. 2009 Apr 1;57(5):467-78
pubmed: 18837051
Clin Chem. 1981 Apr;27(4):562-4
pubmed: 7471422
Neurochem Res. 1982 Dec;7(12):1523-40
pubmed: 6302539
Lab Anim Sci. 1982 Feb;32(1):70-3
pubmed: 7078076
J Neurosci. 2006 Sep 20;26(38):9810-9
pubmed: 16988052
Br Med J. 1967 Jun 3;2(5552):610-1
pubmed: 6025599
Acta Neurol Scand. 1968;44(1):81-90
pubmed: 5706986
Cells. 2019 Feb 24;8(2):
pubmed: 30813473
Am J Clin Nutr. 1998 May;67(5 Suppl):972S-977S
pubmed: 9587138
Nat Genet. 2001 Aug;28(4):350-4
pubmed: 11438811
Acta Neuropathol. 2014 Aug;128(2):247-66
pubmed: 24622774
AJNR Am J Neuroradiol. 2014 Jun;35(6):1085-90
pubmed: 24578278
J Clin Invest. 1947 Jul;26(4):636-40
pubmed: 16695456
Curr Opin Chem Biol. 2008 Apr;12(2):222-8
pubmed: 18342639
Acta Neuropathol. 2009 Oct;118(4):497-504
pubmed: 19597827
Lab Anim. 1998 Apr;32(2):214-8
pubmed: 9587905
J Neural Transm (Vienna). 2011 Mar;118(3):301-14
pubmed: 20809066
Neurology. 1980 Mar;30(3):323-5
pubmed: 7189035
Exp Neurol. 2015 Nov;273:57-68
pubmed: 26247808
Proc Natl Acad Sci U S A. 1999 Sep 14;96(19):10812-7
pubmed: 10485908
N Engl J Med. 2005 Sep 15;353(11):1135-46
pubmed: 16162884
J Biol Chem. 2014 Jan 10;289(2):778-88
pubmed: 24275664
Brain Res. 2015 Feb 19;1598:88-96
pubmed: 25498860
Liver Int. 2005 Jun;25(3):513-7
pubmed: 15910487
J Biol Inorg Chem. 2019 Dec;24(8):1141-1157
pubmed: 31650248
Ann Neurol. 2013 Dec;74(6):848-61
pubmed: 23868451
Wellcome Open Res. 2016 Nov 15;1:10
pubmed: 27996064
Clin Radiol. 2017 Oct;72(10):903.e1-903.e7
pubmed: 28502664
Neurology. 2000 Nov 14;55(9):1340
pubmed: 11087778
J Neurochem. 1991 Mar;56(3):978-82
pubmed: 1704426
J Neurosci. 2015 Mar 25;35(12):4903-16
pubmed: 25810521
Eur J Neurosci. 2001 Sep;14(5):794-8
pubmed: 11576183
Dev Biol. 2001 Nov 1;239(1):46-67
pubmed: 11784018
Am J Physiol. 1990 Feb;258(2 Pt 2):H414-8
pubmed: 2309908
J Lab Clin Med. 1977 Feb;89(2):409-13
pubmed: 833476
Toxicology. 2000 Aug 14;149(1):43-50
pubmed: 10963860
Front Pharmacol. 2014 Aug 25;5:194
pubmed: 25202274
Acta Neurol Psychiatr Belg. 1964 May;64:529-33
pubmed: 14173457
Mov Disord. 2017 Apr;32(4):585-591
pubmed: 28233916
BMC Neurosci. 2008 Apr 05;9:35
pubmed: 18394170
Pediatrics. 1983 Jun;71(6):877-80
pubmed: 6856400
J Neurochem. 2007 Dec;103(5):1730-40
pubmed: 17953660
Pediatr Res. 2003 May;53(5):800-7
pubmed: 12621119
Methods Enzymol. 1988;158:357-64
pubmed: 3374387
Histochemistry. 1993 Jun;99(6):471-5
pubmed: 7691783
J Neuropathol Exp Neurol. 2017 Jun 1;76(6):467-478
pubmed: 28505283