Plasminogen deficiency does not prevent sodium retention in a genetic mouse model of experimental nephrotic syndrome.

Aim: Sodium retention is the hallmark of nephrotic syndrome (NS) and mediated by the proteolytic activation of the epithelial sodium channel (ENaC) by aberrantly filtered serine proteases. Plasmin is highly abundant in nephrotic urine and has been proposed to be the principal serine protease responsible for ENaC activation in NS. However, a proof of the essential role of plasmin in experimental NS is lacking. Methods: We used a genetic mouse model of NS based on an inducible podocin knockout (Bl6-Nphs2tm3.1Antc*Tg(Nphs1-rtTA*3G)8Jhm*Tg(tetO-cre)1Jaw or nphs2Δipod). These mice were crossed with plasminogen deficient mice (Bl6-Plgtm1Jld or plg−/−) to generate double knockout mice (nphs2Δipod*plg−/−). NS was induced after oral doxycycline treatment for 14 days and mice were followed for subsequent 14 days. Results: Uninduced nphs2Δipod*plg−/− mice had normal kidney function and sodium handling. After induction, proteinuria increased similarly in both nphs2Δipod*plg+/+ and nphs2Δipod*plg−/− mice. Western blot revealed the urinary excretion of plasminogen and plasmin in nphs2Δipod*plg+/+ mice which were absent in nphs2Δipod*plg−/− mice. After the onset of proteinuria, amiloride-sensitive natriuresis was increased compared to the uninduced state in both genotypes. Subsequently, urinary sodium excretion dropped in both genotypes leading to an increase in body weight and development of ascites. Treatment with the serine protease inhibitor aprotinin prevented sodium retention in both genotypes. Conclusions: This study shows that mice lacking urinary plasminogen are not protected from ENaC-mediated sodium retention in experimental NS. This points to an essential role of other urinary serine proteases in the absence of plasminogen

Tactile short-term memory in sensory deprived individuals

To verify whether loosing a sense or two has consequences on a spared sensory modality, namely touch, and whether these consequences depend on practice or are biologically determined, we investigated 13 deafblind participants, 16 deaf participants, 15 blind participants, and 13 matched normally sighted and hearing controls on a tactile short-term memory task, using checkerboard matrices of increasing length in which half of the squares were made up of a rough texture and half of a smooth one. Time of execution of a fixed matrix, number of correctly reproduced matrices, largest matrix correctly reproduced and tactile span were recorded. The three groups of sensory- deprived individuals did not differ in any measure, while blind and deaf participants outscored controls in all parameters except time of execution; the difference approached significance for deafblind people compared to controls only in one measure, namely correctly reproduced matrices. In blind and deafblind participants, performance negatively correlated with age of Braille acquisition, the older being the subject when acquiring Braille, the lower the performance, suggesting that practice plays a role. However, the fact that deaf participants, who did not share tactile experience, performed similarly to blind participants and significantly better than controls highlights that practice cannot be the only contribution to better tactile memory