Neuroscience
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Understanding the mechanisms that influence brain excitability and synchronization provides hope that epileptic seizures can be controlled. In this scenario, non-synaptic mechanisms have a critical role in seizure activity. The contribution of ion transporters to the regulation of seizure-like activity has not been extensively studied. ⋯ In addition, bumetanide, a selective inhibitor of neuronal Cl(-) uptake mediated by NKCC1, was used to confirm that the NKCC1 increase effectively contributed to NEA changes in the DG. Furthermore, 7 days after KA, prominent NKCC1 staining was identified in the axon initial segments of granule cells, at the exact site where action potentials are preferentially initiated, which endowed these neurons with increased excitability. Taken together, our data suggest a key role of NKCC1 in NEA in the DG.
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Maternal diabetes during pregnancy may increase the risk of neurodevelopmental disorders in the offspring by increasing inflammation. A major source of inflammatory signaling observed in diabetes is activation of the receptor for advanced glycation end-products (RAGE), and increased RAGE expression has been reported in psychiatric disorders. Thus, we sought to examine whether maternal diabetes creates a proinflammatory state, triggered largely by RAGE signaling, that alters normal brain development and behavior of the offspring. ⋯ In an operant-based strategy set-shifting task, STZ offspring did not differ from controls on an initial visual discrimination or reversal learning but took significantly longer to shift to a new strategy (i.e., set-shift). Insulin replacement with an implantable pellet in the dams reversed the effects of maternal diabetes on RAGE expression, hippocampal excitability, prepulse inhibition and object-place memory, but not anxiety-like behavior or set-shifting. Taken together, these results suggest that chronic maternal hyperglycemia alters normal hippocampal development and behavior of the offspring, effects that may be mediated by increased RAGE signaling in the fetal brain.