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Prenatal exposure to interleukin-6 results in inflammatory neurodegeneration in hippocampus with NMDA/GABA(A) dysregulation and impaired spatial learning

Artikel i vetenskaplig tidskrift
Författare Anne-Maj Samuelsson
Eva Jennische
Hans-Arne Hansson
Agneta Holmäng
Publicerad i Am J Physiol Regul Integr Comp Physiol
Volym 290
Nummer/häfte 5
Sidor R1345-56
Publiceringsår 2006
Publicerad vid Wallenberglaboratoriet
Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi
Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi
Sidor R1345-56
Språk en
Länkar www.ncbi.nlm.nih.gov/entrez/query.f...
Ämnesord Adrenocorticotropic Hormone/blood, Aging/metabolism/psychology, Animals, Apoptosis/drug effects, Astrocytes/pathology, Blotting, Western, Body Weight/physiology, Caspase 3, Caspases/metabolism, DNA, Complementary/biosynthesis/genetics, Female, Glial Fibrillary Acidic Protein/metabolism, Gliosis/chemically induced/pathology, Hippocampus/*pathology, Hydrocortisone/blood, Immunohistochemistry, Inflammation/*pathology, Interleukin-6/*pharmacology, Maze Learning/*physiology, Nerve Degeneration/*pathology, Pregnancy, Prenatal Exposure Delayed Effects, Rats, Rats, Wistar, Receptors, GABA-A/*physiology, Receptors, N-Methyl-D-Aspartate/drug effects/*physiology, Reverse Transcriptase Polymerase Chain Reaction
Ämneskategorier Medicin och Hälsovetenskap

Sammanfattning

During pregnancy, infection or immune responses induce cytokine release, which might influence fetal neurodevelopment, leading to neurodegenerative disease in adulthood. Because the hippocampus is a key area for learning and memory, we evaluated 4- and 24-wk-old rats for the effects of early and late prenatal exposure to interleukin-6 (IL-6) on hippocampal morphology, expression of mRNA for IL-6, the gamma-aminobutyric acid receptor (GABA(Aalpha5)), the NR1 subunit of the N-methyl-D-aspartate receptor, and glial fibrillary acidic protein (GFAP), caspase-3 protein and mRNA levels, and learning abilities. Late exposure increased serum IL-6 and hippocampal expression of IL-6 mRNA at 4 and 24 wk. All adult rats showed neuronal loss in the hilus and astrogliosis; males had losses mainly in the CA2 and CA3 regions, and females in CA1. Expression of GABA(Aalpha5), NR1, and GFAP mRNA increased in late-exposed males and females at 4 and 24 wk. mRNA and protein levels of the apoptosis marker caspase-3 were increased in all late-exposed rats except males at 4 wk. Evaluation of hippocampus-dependent working memory in the Morris water maze at 20 wk of age showed increases in escape latency and time spent near the pool wall in all IL-6 adult rats, especially females. These findings suggest that fetal IL-6 exposure, especially in late pregnancy, leads to increased IL-6 levels in the circulation and hippocampus, abnormalities of hippocampal structural and morphology, and decreased learning during adulthood.

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