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Maternal Hyperhomocysteinemia Induces Neuroinflammation and Neuronal Death in the Rat Offspring Cortex
A D Shcherbitskaia1,2, D S Vasilev3, Yu P Milyutina4
1D.O. Ott Institute of Obstetrics, Gynecology, and Reproductology, St. Petersburg, Russia. nastusiq@gmail.com.
Neurotoxicity Research
|June 7, 2020
Summary
Prenatal exposure to high homocysteine levels in mothers impairs offspring brain development, leading to reduced neurons and increased inflammation. This neuroinflammation impacts cognitive function and brain structure in developing pups.
Area of Science:
- Neuroscience
- Developmental Biology
- Toxicology
Background:
- Maternal hyperhomocysteinemia is a pregnancy complication linked to offspring cognitive deficits.
- Understanding the impact on early brain development is crucial for intervention.
Purpose of the Study:
- To investigate the effects of prenatal hyperhomocysteinemia on the offspring's brain cortex during early development.
- To analyze structural, cellular, apoptotic, and inflammatory changes in the developing brain.
Main Methods:
- Wistar rats were administered methionine during pregnancy to induce hyperhomocysteinemia.
- Cortical tissues from 5- and 20-day-old pups were analyzed using histological, biochemical, and electron microscopy techniques.
- Assessed neuronal/glial cell counts, apoptosis markers (caspase-3), inflammatory cytokines (TNF-α, IL-6, IL-1β), and p38 MAPK phosphorylation.
Main Results:
- Prenatal hyperhomocysteinemia reduced neuronal count (anti-NeuN staining) and increased caspase-3 activity, indicating apoptosis.
- Elevated numbers of astroglial and microglial cells were observed, suggesting neuroinflammation.
- Increased expression of interleukin-1β and p38 MAPK phosphorylation confirmed neuroinflammatory processes.
Conclusions:
- Maternal hyperhomocysteinemia induces significant neurodevelopmental deficits in offspring.
- The study highlights neuroinflammation and neuronal loss as key consequences of impaired embryonic development due to high homocysteine.
- Findings underscore the vulnerability of the developing brain to maternal metabolic disturbances.

