Abstract: —Autophagy and mTOR signaling are fundamental mechanisms that regulate cellular homeostasis and neurogenesis. Alterations in these processes are associated with cognitive dysfunctions and abnormalities in the formation of various brain structures, which are also observed in offspring after prenatal hyperhomo cysteinemia (HHCy). In this study, we investigated the potential impact of maternal HHCy on the activity of autophagy and the mTOR signaling pathway in the brains of fetuses and offspring. The data obtained demon strate the absence of significant changes in the levels of mTOR and its phosphorylated form (p-mTOR), as well as key effector proteins (rpS6, p-rpS6, 4E-BP1 and p-4E-BP1) in the fetal brain at the early embryonic (14th day of development, E14) stages of development and in postnatal ontogeny (5th and 20th days of life, P5 and P20) in the parietal cortex of rats, with the exception of the late embryonic period (E20), which is characterized by a decrease in the level of 4E-BP1 and p-rpS6 (Ser235/236) during maternal death induced by methionine loading. The levels of markers of the main stages of autophagy (ATG13, Beclin-1, Ambra-1, LC3B, p62, LAMP-2) did not change in the embryonic brain (E14 and E20) and the parietal cortex of early postnatal animals (P5), and there was no significant increase in the number of autophagolysosomes and lyso somes in the HHCy. However, an increase in the number of lysosomes, but not autophagosomes, in the pari etal cortex of the brain in P20 animals after prenatal HHCy may be associated with an increase in lysosomal biogenesis. Therefore, the canonical mTOR-dependent change in autophagy in the fetal brain and the pari etal cortex of the offspring after moderate methionine-induced HHCy in the mother is not a significant mechanism for the negative impact on brain tissue formation

Cite: Mikhel A.V. , Vasilev D.S. , Gorbova A.V. , Milyutina Y.P. , Zalozniaia I.V. , Tumanova N.L. , Arutjunyan A.V.
EFFECTS OF PRENATAL HYPERHOMOCYSTEINEMIA ON AUTOPHAGY AND mTOR SIGNALING IN THE DEVELOPING RAT BRAIN
Neurochemical Journal. 2025. V.19. N4. P.902-915. DOI: 10.1134/S1819712425700941

Dates:

Submitted:	Jul 1, 2025
Accepted:	Sep 5, 2025

Identifiers: No identifiers

Citing: Пока нет цитирований

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