ABSTRACT
Systemic and stem cell niche-emanating cytokines and growth factors can promote regeneration, through mitosis. High mitosis, however, predisposes for all types of cancer and, thus, a trade-off exists between regeneration capacity and tissue homeostasis. Here, we study the role of tissue-intrinsic regenerative signaling in stem cell mitosis of adult Drosophila midgut of different genetic backgrounds. We provide evidence of two naturally occurring types of balance between mitosis and enterocyte nucleus growth: one based mostly on stem cell mitosis producing new cells and the other based mostly on the degree of young enterocyte nucleus size increase. Mitosis promotes intestinal host defense to infection, but predisposes for dysplasia in the form of stem cell-like clusters. Enterocyte nucleus growth also promotes host defense, without the drawback of promoting dysplasia. Through quantitative genetics, we identified eiger as an autocrine and paracrine inducer of stem cell mitosis. eiger expression in immature epithelial cells tilts the balance towards mitosis and dysplasia via a positive-feedback loop of highly mitotic stem cells sustaining more small nucleus enterocytes, which in turn supply more Eiger.
Subject(s)
Cell Nucleus/physiology , Drosophila/metabolism , Enterocytes/metabolism , Intestines/cytology , Mitosis , Stem Cells/metabolism , Animals , Animals, Genetically Modified/metabolism , Cyclin E/antagonists & inhibitors , Cyclin E/genetics , Cyclin E/metabolism , Drosophila Proteins/antagonists & inhibitors , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Enterocytes/cytology , Gene Expression Regulation , Intestines/microbiology , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Membrane Proteins/genetics , Membrane Proteins/metabolism , Microscopy, Fluorescence , Pseudomonas aeruginosa/pathogenicity , RNA Interference , Stem Cells/cytologyABSTRACT
OBJECTIVE: The therapeutic mechanism of electroconvulsive therapy (ECT) is unknown. Animal research supports a neurotrophic effect of ECT. To investigate a neurotrophic effect in humans, we examined whether plasma concentration of brain-derived neurotrophic factor (BDNF) increases in patients receiving ECT for major depression. METHOD: We conducted a prospective, self-controlled study of 15 patients with a DSM-IV diagnosis of major depressive episode who were referred for ECT at the University of Maryland Medical Center (Baltimore, Md.) between January 2004 and September 2005. Plasma BDNF concentration was measured by enzyme-linked immunosorbent assay before and during an acute course of ECT. Depression severity was measured using the 21-item Hamilton Rating Scale for Depression (HAM-D). RESULTS: ECT resulted in a significant increase in plasma BDNF (Z = 2.897, p = .004) from a pre-ECT median of 84.9 pg/mL to a post-ECT median of 141.2 pg/mL. This change was accompanied by a significant decrease in HAM-D score (Z = 3.411, p = .001) from a pre-ECT median of 30.0 to a post-ECT median of 9.0. BDNF increased in 13 (86.7%) of 15 subjects. CONCLUSION: This is the first report of an increase in plasma BDNF concentration in patients receiving ECT. These preliminary results encourage further investigation of a neurotrophic mechanism for the antidepressant effect of ECT.