Maternal Hyperhomocysteinemia Induces Neuroinflammation and Neuronal Death in the Rat Offspring Cortex

• Published in: Neurotoxicity research 2020-08, Vol.38 (2), p.408-420
• Main Authors: Shcherbitskaia, A. D., Vasilev, D. S., Milyutina, Yu. P., Tumanova, N. L., Zalozniaia, I. V., Kerkeshko, G. O., Arutjunyan, A. V.
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Cell Biology; Neurobiology; Neurochemistry; Neurology; Neurosciences; Original Article; Pharmacology/Toxicology
• ISSN: 1029-8428; 1476-3524
• DOI: 10.1007/s12640-020-00233-w

Maternal hyperhomocysteinemia is one of the common complications of pregnancy that causes offspring cognitive deficits during postnatal development. In the present work, we evaluated the effect of prenatal hyperhomocysteinemia on structural and ultrastructural organization, neuronal and glial cell number, apoptosis (caspase-3 content and activity), inflammatory markers (tumor necrosis factor-α, interleukin-6, and interleukin-1β), and p38 mitogen–activated protein kinase (p38 MAPK) phosphorylation in the offspring brain cortex in early ontogenesis. Wistar female rats received methionine (0.6 g/kg body weight) by oral administration during pregnancy. Histological and biochemical analyses of 5- and 20-day-old pups’ cortical tissue were performed. Lysosome accumulation and other neurodegenerative changes in neurons of animals with impaired embryonic development were investigated by electron microscopy. Neuronal staining (anti-NeuN) revealed a reduction in neuronal number, accompanied by increasing of caspase-3 active form protein level and activity. Maternal hyperhomocysteinemia also elevated the number of astroglial and microglial cells and increased expression of interleukin-1β and p38 MAPK phosphorylation, which indicates the development of neuroinflammatory processes.