prenatal exposure to IL6

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Subject: Prenatal exposure to interleukin-6 results in inflammatory

neurodegeneration

m J Physiol Regul Integr Comp Physiol 290: R1345-R1356, 2006

DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

Prenatal exposure to interleukin-6 results in inflammatory neurodegeneration in

hippocampus with NMDA/GABAA dysregulation and impaired spatial learning

Anne-Maj sson,1 Eva Jennische,2 Hans-Arne Hansson,2 and Agneta Holmäng1

1Cardiovascular Institute and Wallenberg Laboratory and 2Institute of Anatomy

and Cell Biology, Göteborg University, Sahlgrenska Academy, Göteborg, Sweden

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 -aminobutyric acid receptor (GABAA5), 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 GABAA5,

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 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.

intrauterine exposure; hippocampus; cytokine; spatial learning; water maze

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Address for reprint requests and other correspondence: A.-M. sson, The

Wallenberg Laboratory, Sahlgrenska Univ. Hospital, Göteborg Univ., S-413 45

Göteborg, Sweden (e-mail: anne-maj.samuelsson@...)