412 - Comprehensive analysis of cerebrospinal fluid proteins in fetal growth restriction model: toward identification of early predictive biomarkers for abnormal brain development

Poster Number: 412
Publication Number: 412.237

Atsuto Onoda, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Sanyo-Onoda, Yamaguchi, Japan; Yuma Kitase, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Masahiro Tsuji, Kyoto Women’s University, Kyoto, Kyoto, Japan; Kazuto Ueda, Nagoya University Hospital, Nagoya, Aichi, Japan; Masahiro Hayakawa, Nagoya University Hospital, Nagoya, Aichi, Japan; Yoshiaki Sato, Nagoya University Hospital, Nagoya, Aichi, Japan

Background: Fetal growth restriction (FGR) induces perinatal brain injuries. Thus, it is required to find quantitative biomarkers for early prediction of FGR-induced abnormal brain development. However, critical information on the biomarkers is still unknown. To obtain the information, comprehensive analysis of protein profiles in cerebrospinal fluid (CSF), which sensitively reflect brain damages, is effective approach.

Objective: The current study aimed to identify the biomarkers from CSF protein profiles.

Design/Methods: FGR model was produced by gradual decline of uterus blood flow in pregnant SD rats. The model displays low birth weight and behavioral impairments. CSF, serum, and brain tissues were collected at postnatal day (P) 4-14. CSF protein profiles at P4&5 were acquired by liquid chromatograph/mass spectrometry. The profiles were functionally analyzed using Gene Ontology. Proteins in CSF and serum at P4-14 were quantified by western blotting. Localization of the proteins was assessed by immunofluorescence.

Results: 212 proteins presented significant correlations with birth weight. Functional analysis indicated that the 212 proteins were related to glial cell differentiation, neurogenesis, and neural apoptosis at P4; synapse development, neural network, and behavioral function at P5; inflammation, cell adhesion, and regulation of protein conformation at both P4&5. In FGR pups, disturbance of neural interactions is likely to be induced by abnormal maturation of neural and glial cells due to inflammation and/or protein misfolding. Within the protein groups, expression of 6 proteins were markedly dysregulated by FGR at both P4&5. In the 6 proteins, 4 proteins showed chronic abnormal expression in both CSF and serum. Moreover, abnormal expression of the 4 proteins were observed in neurons and astrocytes; the abnormal expression pattern was depended on cell type, not brain region. The proteins are expected to serve as early biomarkers for FGR-induced brain injuries and key targets to reveal its mechanisms.Conclusion(s): The current study provided novel information on the mechanisms of FGR-induced abnormal brain development and candidates of its biomarkers.
Comprehensive analysis of cerebrospinal fluid proteins in fetal growth restriction model: toward identification of early predictive biomarkers for abnormal brain developmentCV_小野田.pdf