In utero exposure to maternal diabetes impairs nephron progenitor differentiation.

The incidence of diabetes mellitus has significantly increased among women of childbearing age, and it has been shown that prenatal exposure to maternal diabetes increases the risk of associated congenital anomalies of the kidney. Congenital anomalies of the kidney are among the leading causes of chronic kidney disease in children. To better understand the effect of maternal diabetes on kidney development, we analyzed wild-type offspring (DM_Exp) of diabetic Ins2+/C96Y mice (Akita mice). DM_Exp mice at postnatal day 34 have a reduction of ~20% in the total nephron number compared with controls, using the gold standard physical dissector/fractionator method. At the molecular level, the expression of the nephron progenitor markers sine oculis homeobox homolog 2 and Cited1 was increased in DM_Exp kidneys at postnatal day 2. Conversely, the number of early developing nephrons was diminished in DM_Exp kidneys. This was associated with decreased expression of the intracellular domain of Notch1 and the canonical Wnt target lymphoid enhancer binding factor 1. Together, these data suggest that the diabetic intrauterine environment impairs the differentiation of nephron progenitors into nephrons, possibly by perturbing the Notch and Wnt/ß-catenin signaling pathways.

Manipulating memory efficacy affects the behavioral and neural profiles of deterministic learning and decision-making.

When making a decision, we have to identify, collect, and evaluate relevant bits of information to ensure an optimal outcome. How we approach a given choice can be influenced by prior experience. Contextual factors and structural elements of these past decisions can cause a shift in how information is encoded and can in turn influence later decision-making. In this two-experiment study, we sought to manipulate declarative memory efficacy and decision-making in a concurrent discrimination learning task by altering the amount of information to be learned. Subjects learned correct responses to pairs of items across several repetitions of a 50- or 100-pair set and were tested for memory retention. In one experiment, this memory test interrupted learning after an initial encoding experience in order to test for early encoding differences and associate those differences with changes in decision-making. In a second experiment, we used fMRI to probe neural differences between the two list-length groups related to decision-making across learning and assessed subsequent memory retention. We found that a striatum-based system was associated with decision-making patterns when learning a longer list of items, while a medial cortical network was associated with patterns when learning a shorter list. Additionally, the hippocampus was exclusively active for the shorter list group. Altogether, these behavioral, computational, and imaging results provide evidence that multiple types of mnemonic representations contribute to experienced-based decision-making. Moreover, contextual and structural factors of the task and of prior decisions can influence what types of evidence are drawn upon during decision-making.