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Gestational diabetes mellitus (GDM) is a common complication of pregnancy and population health studies have linked it to impaired cognitive performance in the offspring. GDM triggers inflammatory responses, which can critically affect development of neuronal circuitry. We hypothesized that GDM promotes inflammatory responses in the fetus that can disturb fine-tuning of neuronal networks during early development, resulting in lifelong impaired cognitive functions. The cognitive performance of 15 week old offspring exposed to diet induced GDM were assessed. The brain tissue of the 15 week old and neonatal (E20) offspring were analyzed by immunohistochemistry, western blot, and cytokine assay. Cultured microglial responses to elevated glucose and/or fatty acid levels mimicking GDM associated diabetic conditions were analyzed. Our data reveals chronic neuroinflammation in GDM offspring, which combined with deregulation of microglial functions may explain hippocampal CA1 layer neuronal derangement and synaptic degradation that correlates with impaired cognitive performance of GDM offspring. / October 2016