AUTHOR=Nakamura Noriyuki , Ushida Takafumi , Onoda Atsuto , Ueda Kazuto , Miura Ryosuke , Suzuki Toshihiko , Katsuki Satoru , Mizutani Hidesuke , Yoshida Kosuke , Tano Sho , Iitani Yukako , Imai Kenji , Hayakawa Masahiro , Kajiyama Hiroaki , Sato Yoshiaki , Kotani Tomomi 

TITLE=Altered offspring neurodevelopment in an L-NAME-induced preeclampsia rat model

JOURNAL=Frontiers in Pediatrics

VOLUME=Volume 11 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2023.1168173

DOI=10.3389/fped.2023.1168173

ISSN=2296-2360

ABSTRACT=This is a provisional file, not the final typeset articleOffspring of the preeclampsia dam exhibited increased growth restriction at birth (52.5%), but showed postnatal catch-up growth on postnatal day 14. Several behavioral abnormalities including motor development and vestibular function in the neonatal period (negative geotaxis test: p < 0.01); motor coordination and learning skills (rotarod treadmill test: p = 0.01); and memory skills (active avoidance test: p < 0.01) in the juvenile period were observed. NeuN-positive cells in preeclampsia rats were significantly reduced in both the hippocampal dentate gyrus and cerebral cortex (p < 0.01, p < 0.01, respectively). Among the 1,270 proteins in the cerebrospinal fluid identified using liquid chromatography-tandem mass spectrometry, 32 were differentially expressed. Principal component analysis showed that most cerebrospinal fluid samples achieved clear separation between preeclampsia and control rats. Pathway analysis revealed that differentially expressed proteins were associated with endoplasmic reticulum translocation, Rab proteins, and ribosomal proteins, which are involved in various nervous system disorders including autism spectrum disorders, schizophrenia, and Alzheimer's disease.The offspring of the L-NAME-induced preeclampsia model rats exhibited key features of neurodevelopmental abnormalities on behavioral and pathological examinations similar to humans. We found altered cerebrospinal fluid protein profiling in this preeclampsia rat, and the unique protein signatures related to endoplasmic reticulum translocation, Rab proteins, and ribosomal proteins may be associated with subsequent adverse neurodevelopment in the offspring.