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Altered offspring neurodevelopment in an L-NAME-induced preeclampsia rat model
Noriyuki Nakamura1,2, Takafumi Ushida1,3, Atsuto Onoda4
1Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Frontiers in Pediatrics
|July 31, 2023
Summary
Preeclampsia in mothers increases neurodevelopmental disorder risk in offspring. This study used a rat model to identify specific cerebrospinal fluid protein changes linked to these risks.
Area of Science:
- Neuroscience
- Developmental Biology
- Toxicology
Background:
- Preeclampsia is linked to an increased risk of neurodevelopmental disorders in offspring.
- The underlying mechanisms connecting maternal preeclampsia to offspring neurodevelopmental issues remain unclear.
Purpose of the Study:
- To investigate the neurodevelopmental impact of preeclampsia on offspring.
- To identify specific protein signatures in the cerebrospinal fluid of offspring exposed to preeclampsia in utero.
Main Methods:
- A preeclampsia rat model was induced using N-nitro-L-arginine methyl ester (L-NAME).
- Offspring underwent behavioral tests, immunohistochemistry (NeuN staining), and cerebrospinal fluid proteome analysis.
- Liquid chromatography-tandem mass spectrometry was used for protein identification and quantification.
Main Results:
- Offspring exhibited growth restriction, behavioral abnormalities (motor, learning, memory), and reduced neuronal markers (NeuN).
- Proteomic analysis revealed 32 differentially expressed proteins in cerebrospinal fluid.
- Altered proteins were associated with endoplasmic reticulum translocation, Rab proteins, and ribosomal proteins.
Conclusions:
- The L-NAME-induced preeclampsia rat model replicates human neurodevelopmental abnormalities.
- Cerebrospinal fluid protein profiling identified unique signatures potentially linked to adverse neurodevelopment.
- These findings suggest specific protein pathways may mediate the effects of preeclampsia on offspring brain development.
