Human Urine as a Noninvasive Source of Kidney Cells

Urine represents an unlimited source of patient-specific kidney cells that can be harvested noninvasively. Urine derived podocytes and proximal tubule cells have been used to study disease mechanisms and to screen for novel drug therapies in a variety of human kidney disorders. The urinary kidney stem/progenitor cells and extracellular vesicles, instead, might be promising for therapeutic treatments of kidney injury. The greatest advantages of urine as a source of viable cells are the easy collection and less complicated ethical issues. However, extensive characterization and in vivo studies still have to be performed before the clinical use of urinederived kidney progenitors

Neurogenomic Evidence for a Shared Mechanism of the Antidepressant Effects of Exercise and Chronic Fluoxetine in Mice

Several different interventions improve depressed mood, including medication and environmental factors such as regular physical exercise. The molecular pathways underlying these effects are still not fully understood. In this study, we sought to identify shared mechanisms underlying antidepressant interventions. We studied three groups of mice: mice treated with a widely used antidepressant drug – fluoxetine, mice engaged in voluntary exercise, and mice living in an enriched environment. The hippocampi of treated mice were investigated at the molecular and cellular levels. Mice treated with fluoxetine and mice who exercised daily showed, not only similar antidepressant behavior, but also similar changes in gene expression and hippocampal neurons. These changes were not observed in mice with environmental enrichment. An increase in neurogenesis and dendritic spine density was observed following four weeks of fluoxetine treatment and voluntary exercise. A weighted gene co-expression network analysis revealed four different modules of co-expressed genes that were correlated with the antidepressant effect. This network analysis enabled us to identify genes involved in the molecular pathways underlying the effects of fluoxetine and exercise. The existence of both neuronal and gene expression changes common to antidepressant drug and exercise suggests a shared mechanism underlying their effect. Further studies of these findings may be used to uncover the molecular mechanisms of depression, and to identify new avenues of therapy

Human Urine as a Noninvasive Source of Kidney Cells

Urine represents an unlimited source of patient-specific kidney cells that can be harvested noninvasively. Urine derived podocytes and proximal tubule cells have been used to study disease mechanisms and to screen for novel drug therapies in a variety of human kidney disorders. The urinary kidney stem/progenitor cells and extracellular vesicles, instead, might be promising for therapeutic treatments of kidney injury. The greatest advantages of urine as a source of viable cells are the easy collection and less complicated ethical issues. However, extensive characterization and in vivo studies still have to be performed before the clinical use of urine-derived kidney progenitors

Validation by real-time PCR of three genes that show differential expression in the microarray analysis.

<p>The expression of Nptx2, Bdnf and Plekha2 is shown for the fluoxetine and exercise groups relative to control. (A) Relative expression based on (A) expression arrays and (B) real-time PCR. Values are means ± SEM. *<i>P</i><0.05, **<i>P</i><0.01, ***<i>P</i><0.001.</p

Hippocampal gene expression profiles in response to different antidepressant treatments.

<p>(A) Changes in expression following exercise compared with the changes in the fluoxetine treated group. Each point is the average expression level of the treated group divided by the average expression level in the control group for one of the 87 genes showing significant differential expression. The Y and X axes are on a log scale, base 2. The line is the best fit linear regression. (B) Changes in expression in an enriched environment as a function of the changes in the fluoxetine treated group. (C) Changes in expression for 36 genes (out of 87) with the highest fold change following chronic fluoxetine treatment compared to controls. (D) Comparison of the effect of fluoxetine on gene expression in the current study with the results obtained by Miller et al. (2008) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035901#pone.0035901-Miller1" target="_blank">[17]</a>.</p

Modules of co-expressed genes associated with antidepressant interventions.

1<p>correlation between module eigengene and antidepressant interventions (exercise and fluoxetine).</p><p>In bold are the gene with the highest module membership score.</p

DCX staining and dendritic spine density in the hippocampus.

<p>(A and B) The exercise and fluoxetine groups showed more immature neurons in the dentate gyrus compared to controls. (C and D) Golgi staining images reveal higher level of dendritic spine density in the hippocampus (CA1 region) in the exercise and fluoxetine groups. Values are means ± SEM. *<i>P</i><0.05, ***<i>P</i><0.001. Scale bar show 200 µm (A) and 10 µm (B).</p

Antidepressant-like behavior in mice engaged in voluntary exercise for 28 days (n = 8).

<p>A series of antidepressant-like behavioral tests were conducted. (A) There was no significant difference in the activity in the open field test. (B) Exercise group showed lower levels of digging activity in a new cage with a 5 cm layer of sawdust bedding. (C) In the novelty suppressed feeding test, the exercise group increased the time spent in eating in a rat odor cage compared to controls. No significant differences between the groups in food consumption at the home cage. (D) In the novelty induced hypophagia test, the exercise group spent more time drinking sweet milk under bright lighting cage condition, but no significant differences were observed under dim lighting cage conditions. Values are means ± SEM. *<i>P</i><0.05, **<i>P</i><0.01.</p

Cell survival and neurogenesis in the four different groups.

<p>BrdU (200 mg/kg) was injected into all mice before dividing them into different groups. After 28 days, brain tissues (hippocampus) were stained for BrdU and NeuN (A–C). The exercise and fluoxetine groups, but not the enriched environment group, showed higher number of BrdU and NeuN positive cells in the dentate gyrus (D) compared to the control group. Values are means ± SEM. **<i>P</i><0.01, ***<i>P</i><0.001.</p