Cellular distribution of transferrin immunoreactivity in the developing rat brain

doi:10.1016/0304-3940(87)90557-X

Neuroscience Letters

Volume 78, Issue 1, 9 July 1987, Pages 35-40

https://doi.org/10.1016/0304-3940(87)90557-X Get rights and content

Abstract

The cellular distribution of immunoreactive transferrin has previously been studied in adult rat brain with the conclusion that transferrin is largely confined to oligodendrocytes, although studies in the developing rodent brain indicated some staining of neurons. Detailed investigations of a wider range of ages than studied earlier have shown that in the developing rat brain, transferrin is not only present in oligodendrocytes but also in other glial cell types and in neurons and endothelial cells. The preponderant cell type which is positive for transferrin and its regional distribution are, however, related to the age of the animal except in most circumventricular organs in which strong transferrin immunoreactivity was seen throughout the developmental period studied.

References (18)

J.R. Connor et al.
The distribution of transferrin immunoreactivity in the rat central nervous system
Brain Res.
(1986)
K.M. Dziegielewska et al.
Synthesis of plasma proteins by rat fetal brain choroid plexus
Int. J. Dev. Neurosci.
(1984)
K.M. Dziegielewska et al.
Messenger ribonucleic acid (mRNA) from developing rat cerebellum directs in vitro synthesis of plasma proteins
Dev. Brain Res.
(1985)
K.M. Dziegielewska et al.
Synthesis of plasma proteins in fetal, adult and neoplastic human brain tissue
Dev. Biol.
(1986)
M.J. Levin et al.
Expression of the transferrin gene during development of non-hepatic tissues
Biochem. Biophys. Res. Commun.
(1984)
G.S. McKnight et al.
Transferrin gene expression
Regulation of mRNA transcription in chick liver by steroid hormones and iron deficiency
J. Biol. Chem.
(1980)
H. New et al.
Transferrin in fetal rat brain and cerebrospinal fluid
Int. J. Dev. Neurosci.
(1983)
T.H. Oh et al.
Immunocytochemical distribution of transferrin and its receptor in the developing chicken nervous system
Dev. Brain Res.
(1986)
N.R. Saunders
Ontogeny of the blood-brain barrier
Exp. Eye Res.
(1977)

There are more references available in the full text version of this article.

Cited by (20)

Parkinson's disease: Alterations in iron and redox biology as a key to unlock therapeutic strategies
2021, Redox Biology
Citation Excerpt :
In fact, while transferrin has been identified in oligodendrocytes, it has been reported that there is no transferrin receptor 1 expression in these cells [292]. However, this does not agree with reports of transferrin being found within oligodendrocytes in humans, rats and chickens [293–296]. This latter observation could suggest transferrin within endosomes, or alternatively, transferrin being synthesized by these cells.
A plethora of studies indicate that iron metabolism is dysregulated in Parkinson's disease (PD). The literature reveals well-documented alterations consistent with established dogma, but also intriguing paradoxical observations requiring mechanistic dissection. An important fact is the iron loading in dopaminergic neurons of the substantia nigra pars compacta (SNpc), which are the cells primarily affected in PD. Assessment of these changes reveal increased expression of proteins critical for iron uptake, namely transferrin receptor 1 and the divalent metal transporter 1 (DMT1), and decreased expression of the iron exporter, ferroportin-1 (FPN1). Consistent with this is the activation of iron regulator protein (IRP) RNA-binding activity, which is an important regulator of iron homeostasis, with its activation indicating cytosolic iron deficiency. In fact, IRPs bind to iron-responsive elements (IREs) in the 3ꞌ untranslated region (UTR) of certain mRNAs to stabilize their half-life, while binding to the 5ꞌ UTR prevents translation. Iron loading of dopaminergic neurons in PD may occur through these mechanisms, leading to increased neuronal iron and iron-mediated reactive oxygen species (ROS) generation. The “gold standard” histological marker of PD, Lewy bodies, are mainly composed of α-synuclein, the expression of which is markedly increased in PD. Of note, an atypical IRE exists in the α-synuclein 5ꞌ UTR that may explain its up-regulation by increased iron. This dysregulation could be impacted by the unique autonomous pacemaking of dopaminergic neurons of the SNpc that engages L-type Ca⁺² channels, which imparts a bioenergetic energy deficit and mitochondrial redox stress. This dysfunction could then drive alterations in iron trafficking that attempt to rescue energy deficits such as the increased iron uptake to provide iron for key electron transport proteins. Considering the increased iron-loading in PD brains, therapies utilizing limited iron chelation have shown success. Greater therapeutic advancements should be possible once the exact molecular pathways of iron processing are dissected.
Aluminum
2012, Veterinary Toxicology: Basic and Clinical Principles
Aluminum
2012, Veterinary Toxicology
Aluminum
2007, Veterinary Toxicology: Basic and Clinical Principles
Aluminum
2007, Veterinary Toxicology
Transcytosis of protein through the mammalian cerebral epithelium and endothelium. III. Receptor-mediated transcytosis through the blood-brain barrier of blood-borne transferrin and antibody against the transferrin receptor
1996, Experimental Neurology
Diferric-transferrin (Tf; 80K mol. wt.) and the OX26 antibody (150K mol. wt.) against the transferrin receptor (TfR) were evaluated in the rat at light and ultrastructural levels as potential vehicles for the blood to brain transcellular transfer (transcytosis) of native horseradish peroxidase (40K mol. wt.), which by itself does not cross the blood–brain barrier (BBB). OX26, the Fab fragment of OX26 (50K mol. wt.), and Tf complexed to two ferric ions were conjugated to HRP irreversibly in a 1:1 molar ratio. The indirect immunoperoxidase technique with OX26 as the monoclonal primary antibody applied to the surface of cryostat sections or delivered intravenously to the live rat revealed TfRs on BBB capillaries, arterioles, and venules; TfRs were absent on non-BBB vessels supplying the circumventricular organs (i.e., median eminence, choroid plexus). OX26–HRP and OX26(Fab)–HRP delivered intravenously and diferric-Tf–HRP administered into the carotid artery labeled BBB vessels throughout the CNS without discernible disruption of the BBB or extravasation of the blood-borne probes into the brain parenchyma. No reaction product for the probes was observed in sites deficient in a BBB. Each of the macromolecular conjugates was endocytosed by BBB endothelia and labeled presumptive endocytic vesicles, endosomes, and dense bodies. OX26–HRP and Tf–HRP, but not OX26(Fab)–HRP, appeared to undergo transcytosis through BBB endothelia for subsequent labeling of perivascular cells. Distinct differences in the intracellular and extracellular distributions between OX26–HRP and Tf–HRP were identified: (1) endocytosis and sequestration of blood-borne OX26–HRP within BBB endothelia were more prominent than those for diferric-Tf–HRP; (2) only OX26–HRP labeled the Golgi complex in BBB endothelia; (3) peroxidase labeling of CNS perivascular clefts and perivascular cells in rats receiving diferric-Tf–HRP was conspicuous at less than 1 h postinjection but not so in rats with blood-borne OX26–HRP at 5 min through 6 h postinjection; and (4) peroxidase-labeled CNS neurons and glial cells were identified readily in rats receiving diferric-Tf–HRP. The results suggest that the receptor-mediated, transendothelial transfer of Tf–HRP from blood to brain is more efficient and direct than that of OX26–HRP. Labeling of the Golgi complex in BBB endothelia with blood-borne OX26–HRP implies that the transendothelial transfer of OX26–HRP follows intraendothelial pathways associated with the process of adsorptive transcytosis. A diagram is provided depicting the possible intracellular and transcellular pathways within BBB endothelia available to blood-borne diferric-Tf and OX26 as vectors for delivery into the CNS of non-lipid-soluble macromolecules that otherwise are denied entry by the blood–brain fluid barriers.

View all citing articles on Scopus

View full text

Cellular distribution of transferrin immunoreactivity in the developing rat brain

Abstract

Brain Res.

Int. J. Dev. Neurosci.

Dev. Brain Res.

Dev. Biol.

Biochem. Biophys. Res. Commun.

J. Biol. Chem.

Int. J. Dev. Neurosci.

Dev. Brain Res.

Exp. Eye Res.