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Characterization of choroid plexus in the preterm rabbit pup following subcutaneous administration of recombinant human IGF-1/IGFBP-3

Ortenlöf, Niklas LU ; Vallius, Suvi LU ; Karlsson, Helena LU ; Ekström, Claes LU orcid ; Kristiansson, Amanda LU ; Holmqvist, Bo ; Göransson, Olga LU orcid ; Vaváková, Magdaléna LU ; Rydén, Martin LU orcid and Carey, Galen , et al. (2023) In Fluids and Barriers of the CNS 20(1).
Abstract

Insulin-like growth factor-1 (IGF-1) is essential for normal brain development and regulates essential processes of vascular maturation and stabilization. Importantly, preterm birth is associated with reduced serum levels of IGF-1 as compared to in utero levels. Using a preterm rabbit pup model, we investigated the uptake of systemic recombinant human (rh) IGF-1 in complex with its main binding protein IGF-binding protein 3 (BP-3) to the brain parenchyma via the choroid plexus. Five hours after subcutaneous administration, labeled rhIGF-1/rhIGFBP-3 displayed a widespread presence in the choroid plexus of the lateral and third ventricle, however, to a less degree in the fourth, as well as in the perivascular and subarachnoid space. We... (More)

Insulin-like growth factor-1 (IGF-1) is essential for normal brain development and regulates essential processes of vascular maturation and stabilization. Importantly, preterm birth is associated with reduced serum levels of IGF-1 as compared to in utero levels. Using a preterm rabbit pup model, we investigated the uptake of systemic recombinant human (rh) IGF-1 in complex with its main binding protein IGF-binding protein 3 (BP-3) to the brain parenchyma via the choroid plexus. Five hours after subcutaneous administration, labeled rhIGF-1/rhIGFBP-3 displayed a widespread presence in the choroid plexus of the lateral and third ventricle, however, to a less degree in the fourth, as well as in the perivascular and subarachnoid space. We found a time-dependent uptake of IGF-1 in cerebrospinal fluid, decreasing with postnatal age, and a translocation of IGF-1 through the choroid plexus. The impact of systemic rhIGF-1/rhIGFBP-3 on IGF-1 receptor activation in the choroid plexus decreased with postnatal age, correlating with IGF-1 uptake in cerebrospinal fluid. In addition, choroid plexus gene expression was observed to increase with postnatal age. Moreover, using choroid plexus in vitro cell cultures, gene expression and protein synthesis were further investigated upon rhIGF-1/rhIGFBP-3 stimulation as compared to rhIGF-1 alone, and found not to be differently altered. Here, we characterize the uptake of systemic rhIGF-1/rhIGFBP-3 to the preterm brain, and show that the interaction between systemic rhIGF-1/rhIGFBP-3 and choroid plexus varies over time.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Blood-cerebrospinal fluid barrier, Cerebrospinal fluid, Choroid plexus, Immature brain, Insulin-like growth factor-1, Insulin-like growth factor-1 receptor, Preterm infant, Preterm rabbit pup, Serum, Ventricles
in
Fluids and Barriers of the CNS
volume
20
issue
1
article number
59
publisher
BioMed Central (BMC)
external identifiers
  • scopus:85168063765
  • pmid:37582792
ISSN
2045-8118
DOI
10.1186/s12987-023-00460-1
language
English
LU publication?
yes
id
210f84dc-4ebf-4fd8-99e6-3dcc53d20a66
date added to LUP
2023-10-19 09:26:17
date last changed
2025-01-25 07:11:04
@article{210f84dc-4ebf-4fd8-99e6-3dcc53d20a66,
  abstract     = {{<p>Insulin-like growth factor-1 (IGF-1) is essential for normal brain development and regulates essential processes of vascular maturation and stabilization. Importantly, preterm birth is associated with reduced serum levels of IGF-1 as compared to in utero levels. Using a preterm rabbit pup model, we investigated the uptake of systemic recombinant human (rh) IGF-1 in complex with its main binding protein IGF-binding protein 3 (BP-3) to the brain parenchyma via the choroid plexus. Five hours after subcutaneous administration, labeled rhIGF-1/rhIGFBP-3 displayed a widespread presence in the choroid plexus of the lateral and third ventricle, however, to a less degree in the fourth, as well as in the perivascular and subarachnoid space. We found a time-dependent uptake of IGF-1 in cerebrospinal fluid, decreasing with postnatal age, and a translocation of IGF-1 through the choroid plexus. The impact of systemic rhIGF-1/rhIGFBP-3 on IGF-1 receptor activation in the choroid plexus decreased with postnatal age, correlating with IGF-1 uptake in cerebrospinal fluid. In addition, choroid plexus gene expression was observed to increase with postnatal age. Moreover, using choroid plexus in vitro cell cultures, gene expression and protein synthesis were further investigated upon rhIGF-1/rhIGFBP-3 stimulation as compared to rhIGF-1 alone, and found not to be differently altered. Here, we characterize the uptake of systemic rhIGF-1/rhIGFBP-3 to the preterm brain, and show that the interaction between systemic rhIGF-1/rhIGFBP-3 and choroid plexus varies over time.</p>}},
  author       = {{Ortenlöf, Niklas and Vallius, Suvi and Karlsson, Helena and Ekström, Claes and Kristiansson, Amanda and Holmqvist, Bo and Göransson, Olga and Vaváková, Magdaléna and Rydén, Martin and Carey, Galen and Barton, Norman and Ley, David and Gram, Magnus}},
  issn         = {{2045-8118}},
  keywords     = {{Blood-cerebrospinal fluid barrier; Cerebrospinal fluid; Choroid plexus; Immature brain; Insulin-like growth factor-1; Insulin-like growth factor-1 receptor; Preterm infant; Preterm rabbit pup; Serum; Ventricles}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Fluids and Barriers of the CNS}},
  title        = {{Characterization of choroid plexus in the preterm rabbit pup following subcutaneous administration of recombinant human IGF-1/IGFBP-3}},
  url          = {{http://dx.doi.org/10.1186/s12987-023-00460-1}},
  doi          = {{10.1186/s12987-023-00460-1}},
  volume       = {{20}},
  year         = {{2023}},
}