Differential Brain and Cerebrospinal Fluid Proteomic Responses to Acute Prenatal Endotoxin Exposure
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Differential Brain and Cerebrospinal Fluid Proteomic Responses to Acute Prenatal Endotoxin Exposure. / Muk, Tik; Stensballe, Allan; Dmytriyeva, Oksana; Brunse, Anders; Jiang, Ping Ping; Thymann, Thomas; Sangild, Per Torp; Pankratova, Stanislava.
I: Molecular Neurobiology, Bind 59, 2022, s. 2204–2218.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Differential Brain and Cerebrospinal Fluid Proteomic Responses to Acute Prenatal Endotoxin Exposure
AU - Muk, Tik
AU - Stensballe, Allan
AU - Dmytriyeva, Oksana
AU - Brunse, Anders
AU - Jiang, Ping Ping
AU - Thymann, Thomas
AU - Sangild, Per Torp
AU - Pankratova, Stanislava
N1 - Publisher Copyright: © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2022
Y1 - 2022
N2 - Chorioamnionitis (CA) is a risk factor for preterm birth and is associated with neurodevelopmental delay and cognitive disorders. Prenatal inflammation-induced brain injury may resolve during the immediate postnatal period when rapid brain remodeling occurs. Cerebrospinal fluid (CSF) collected at birth may be a critical source of predictive biomarkers. Using pigs as a model of preterm infants exposed to CA, we hypothesized that prenatal lipopolysaccharide (LPS) exposure induces proteome changes in the CSF and brain at birth and postnatally. Fetal piglets (103 days gestation of full-term at 117 days) were administered intra-amniotic (IA) lipopolysaccharide (LPS) 3 days before preterm delivery by caesarian section. CSF and brain tissue were collected on postnatal Days 1 and 5 (P1 and P5). CSF and hippocampal proteins were profiled by LC–MS-based quantitative proteomics. Neuroinflammatory responses in the cerebral cortex, periventricular white matter and hippocampus were evaluated by immunohistochemistry, and gene expression was evaluated by qPCR. Pigs exposed to LPS in utero showed changes in CSF protein levels at birth but not at P5. Complement protein C3, hemopexin, vasoactive intestinal peptide, carboxypeptidase N subunit 2, ITIH1, and plasminogen expression were upregulated in the CSF, while proteins associated with axon growth and synaptic functions (FGFR1, BASP1, HSPD1, UBER2N, and RCN2), adhesion (talin1), and neuronal survival (Atox1) were downregulated. Microglia, but not astrocytes, were activated by LPS at P5 in the hippocampus but not in other brain regions. At this time, marginal increases in complement protein C3, LBP, HIF1a, Basp1, Minpp1, and FGFR1 transcription indicated hippocampal proinflammatory responses. In conclusion, few days exposure to endotoxin prenatally induce proteome changes in the CSF and brain at birth, but most changes resolve a few days later. The developing hippocampus has high neuronal plasticity in response to perinatal inflammation. Changes in CSF protein expression at birth may predict later structural brain damage in preterm infants exposed to variable types and durations of CA-related inflammation in utero.
AB - Chorioamnionitis (CA) is a risk factor for preterm birth and is associated with neurodevelopmental delay and cognitive disorders. Prenatal inflammation-induced brain injury may resolve during the immediate postnatal period when rapid brain remodeling occurs. Cerebrospinal fluid (CSF) collected at birth may be a critical source of predictive biomarkers. Using pigs as a model of preterm infants exposed to CA, we hypothesized that prenatal lipopolysaccharide (LPS) exposure induces proteome changes in the CSF and brain at birth and postnatally. Fetal piglets (103 days gestation of full-term at 117 days) were administered intra-amniotic (IA) lipopolysaccharide (LPS) 3 days before preterm delivery by caesarian section. CSF and brain tissue were collected on postnatal Days 1 and 5 (P1 and P5). CSF and hippocampal proteins were profiled by LC–MS-based quantitative proteomics. Neuroinflammatory responses in the cerebral cortex, periventricular white matter and hippocampus were evaluated by immunohistochemistry, and gene expression was evaluated by qPCR. Pigs exposed to LPS in utero showed changes in CSF protein levels at birth but not at P5. Complement protein C3, hemopexin, vasoactive intestinal peptide, carboxypeptidase N subunit 2, ITIH1, and plasminogen expression were upregulated in the CSF, while proteins associated with axon growth and synaptic functions (FGFR1, BASP1, HSPD1, UBER2N, and RCN2), adhesion (talin1), and neuronal survival (Atox1) were downregulated. Microglia, but not astrocytes, were activated by LPS at P5 in the hippocampus but not in other brain regions. At this time, marginal increases in complement protein C3, LBP, HIF1a, Basp1, Minpp1, and FGFR1 transcription indicated hippocampal proinflammatory responses. In conclusion, few days exposure to endotoxin prenatally induce proteome changes in the CSF and brain at birth, but most changes resolve a few days later. The developing hippocampus has high neuronal plasticity in response to perinatal inflammation. Changes in CSF protein expression at birth may predict later structural brain damage in preterm infants exposed to variable types and durations of CA-related inflammation in utero.
KW - Cerebrospinal fluid
KW - Chorioamnionitis
KW - Hippocampus
KW - Inflammation
KW - Neurodevelopment
KW - Preterm pig
U2 - 10.1007/s12035-022-02753-2
DO - 10.1007/s12035-022-02753-2
M3 - Journal article
C2 - 35064541
AN - SCOPUS:85123257621
VL - 59
SP - 2204
EP - 2218
JO - Molecular Neurobiology
JF - Molecular Neurobiology
SN - 0893-7648
ER -
ID: 291124343