TY - JOUR

T1 - Prenatal Hyperhomocysteinemia Induces Glial Activation and Alters Neuroinflammatory Marker Expression in Infant Rat Hippocampus

AU - Shcherbitskaia, Anastasiia D.

AU - Vasilev, Dmitrii S.

AU - Milyutina, Yulia P.

AU - Tumanova, Natalia L.

AU - Mikhel, Anastasiia V.

AU - Zalozniaia, Irina V.

AU - Arutjunyan, Alexander V.

PY - 2021/6/18

Y1 - 2021/6/18

N2 - Maternal hyperhomocysteinemia is one of the common complications of pregnancy that causes offspring cognitive deficits during postnatal development. In this study, we investigated the effect of prenatal hyperhomocysteinemia (PHHC) on inflammatory, glial activation, and neuronal cell death markers in the hippocampus of infant rats. Female Wistar rats received L-methionine (0.6 g/kg b.w.) by oral administration during pregnancy. On postnatal days 5 and 20, the offspring's hippocampus was removed to perform histological and biochemical studies. After PHHC, the offspring exhibited increased brain interleukin-1β and interleukin-6 levels and glial activation, as well as reduced anti-inflammatory interleukin-10 level in the hippocampus. Additionally, the activity of acetylcholinesterase was increased in the hippocampus of the pups. Exposure to PHHC also resulted in the reduced number of neurons and disrupted neuronal ultrastructure. At the same time, no changes in the content and activity of caspase-3 were found in the hippocampus of the pups. In conclusion, our findings support the hypothesis that neuroinflammation and glial activation could be involved in altering the hippocampus cellular composition following PHHC, and these alterations could be associated with cognitive disorders later in life.

AB - Maternal hyperhomocysteinemia is one of the common complications of pregnancy that causes offspring cognitive deficits during postnatal development. In this study, we investigated the effect of prenatal hyperhomocysteinemia (PHHC) on inflammatory, glial activation, and neuronal cell death markers in the hippocampus of infant rats. Female Wistar rats received L-methionine (0.6 g/kg b.w.) by oral administration during pregnancy. On postnatal days 5 and 20, the offspring's hippocampus was removed to perform histological and biochemical studies. After PHHC, the offspring exhibited increased brain interleukin-1β and interleukin-6 levels and glial activation, as well as reduced anti-inflammatory interleukin-10 level in the hippocampus. Additionally, the activity of acetylcholinesterase was increased in the hippocampus of the pups. Exposure to PHHC also resulted in the reduced number of neurons and disrupted neuronal ultrastructure. At the same time, no changes in the content and activity of caspase-3 were found in the hippocampus of the pups. In conclusion, our findings support the hypothesis that neuroinflammation and glial activation could be involved in altering the hippocampus cellular composition following PHHC, and these alterations could be associated with cognitive disorders later in life.

KW - cytokines

KW - glial reaction

KW - hippocampus

KW - homocysteine

KW - neurodegeneration

KW - neuroinflammation

KW - HOMOCYSTEINE

KW - NERVOUS-SYSTEM

KW - SIGNAL-TRANSDUCTION PATHWAYS

KW - OXIDATIVE STRESS

KW - DNA METHYLATION

KW - P38 MAPK

KW - S-ADENOSYLHOMOCYSTEINE

KW - BIOGENIC-AMINES

KW - GENE-EXPRESSION

KW - UP-REGULATION

KW - Cytokines

KW - Neuroinflammation

KW - Neurodegeneration

KW - Glial reaction

KW - Homocysteine

KW - Hippocampus

UR - http://www.scopus.com/inward/record.url?scp=85110264377&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/880689c6-e76e-35dc-9bd5-6d5c95dcd359/

U2 - 10.3390/cells10061536

DO - 10.3390/cells10061536

M3 - Article

C2 - 34207057

AN - SCOPUS:85110264377

VL - 10

JO - Cells

JF - Cells

SN - 2073-4409

IS - 6

M1 - 1536

ER -