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

• DOI: 10.3389/fped.2023.1168173
• Publication Date: 2023-07-13T15:15:03Z
• Authors: Noriyuki Nakamura; Takafumi Ushida; Atsuto Onoda; Kazuto Ueda; Ryosuke Miura; Toshihiko Suzuki; Satoru Katsuki; Hidesuke Mizutani; Kosuke Yoshida; Sho Tano; Yukako Iitani; Kenji Imai; Masahiro Hayakawa; Hiroaki Kajiyama; Yoshiaki Sato; Tomomi Kotani
• Keywords: NeuN; Intraperitoneal injection

To investigate the mechanism underlying increased risk of subsequent neurodevelopmental disorders in children born to mothers with preeclampsia, we evaluated neurodevelopment offspring a preeclampsia rat model induced by administration N-nitro-L-arginine methyl ester (L-NAME) and identified unique protein signatures cerebrospinal fluid.Pregnant rats received an intraperitoneal injection L-NAME (250 mg/kg/day) during gestational days 15-20 establish model. Behavioral experiments (negative geotaxis, open-field, rotarod treadmill, active avoidance tests), immunohistochemistry [anti-neuronal nuclei (NeuN) staining hippocampal dentate gyrus cerebral cortex on postnatal day 70], proteome analysis fluid 5 were performed male offspring.Offspring dam exhibited growth restriction at birth (52.5%), but showed catch-up 14. Several behavioral abnormalities including motor development vestibular function geotaxis test: p < 0.01) neonatal period; coordination learning skills (rotarod treadmill = 0.01); memory (active juvenile period observed. NeuN-positive cells significantly reduced both (p 0.01, respectively). Among 1270 proteins using liquid chromatography-tandem mass spectrometry, 32 differentially expressed. Principal component that most samples achieved clear separation between control rats. Pathway revealed expressed associated endoplasmic reticulum translocation, Rab proteins, ribosomal which are involved various nervous system autism spectrum disorders, schizophrenia, Alzheimer's disease.The L-NAME-induced key features pathological examinations similar humans. We found altered profiling this rat, related may be adverse offspring.