Social stress induces neurovascular pathology promoting depression

Studies suggest that heightened peripheral inflammation contributes to the pathogenesis of major depressive disorder. We investigated the effect of chronic social defeat stress, a mouse model of depression, on blood–brain barrier (BBB) permeability and infiltration of peripheral immune signals. We found reduced expression of the endothelial cell tight junction protein claudin-5 (Cldn5) and abnormal blood vessel morphology in nucleus accumbens (NAc) of stress-susceptible but not resilient mice. CLDN5 expression was also decreased in NAc of depressed patients. Cldn5 downregulation was sufficient to induce depression-like behaviors following subthreshold social stress whereas chronic antidepressant treatment rescued Cldn5 loss and promoted resilience. Reduced BBB integrity in NAc of stress-susceptible or mice injected with adeno-associated virus expressing shRNA against Cldn5 caused infiltration of the peripheral cytokine interleukin-6 (IL-6) into brain parenchyma and subsequent expression of depression-like behaviors. These findings suggest that chronic social stress alters BBB integrity through loss of tight junction protein Cldn5, promoting peripheral IL-6 passage across the BBB and depressio

Pluses and minuses of ammonium and nitrate uptake and assimilation by phytoplankton and implications for productivity and community composition, with emphasis on nitrogen-enriched conditions

Anthropogenic activities are altering total nutrient loads to many estuaries and freshwaters, resulting in high loads not only of total nitrogen (N), but in some cases, of chemically reduced forms, notably NH4+. Long thought to be the preferred form of N for phytoplankton uptake, NH4+ may actually suppress overall growth when concentrations are sufficiently high. NH4+ has been well known to be inhibitory or repressive for NO3- uptake and assimilation, but the concentrations of NH4+ that promote vs. repress NO3- uptake, assimilation, and growth in different phytoplankton groups and under different growth conditions are not well understood. Here, we review N metabolism first in a "generic" eukaryotic cell, and the contrasting metabolic pathways and regulation of NH4+ and NO3- when these substrates are provided individually under equivalent growth conditions. Then the metabolic interactions of these substrates are described when both are provided together, emphasizing the cellular challenge of balancing nutrient acquisition with photosynthetic energy balance in dynamic environments. Conditions under which dissipatory pathways such as dissimilatory NO3-/ NO2- reduction to NH4+ and photorespiration that may lead to growth suppression are highlighted. While more is known about diatoms, taxon-specific differences in NH4+ and NO3- metabolism that may contribute to changes in phytoplankton community composition when the composition of the N pool changes are presented. These relationships have important implications for harmful algal blooms, development of nutrient criteria for management, and modeling of nutrient uptake by phytoplankton, particularly in conditions where eutrophication is increasing and the redox state of N loads is changing.</p