Diazepam Binding Inhibitor Promotes Stem Cell Expansion Controlling Environment-Dependent Neurogenesis.
Plasticity of adult neurogenesis supports adaptation to environmental changes. The identification of molecular mediators that signal these changes to neural progenitors in the niche has remained elusive. Here we report that diazepam binding inhibitor (DBI) is crucial in supporting an adaptive mechanism in response to changes in the environment. We provide evidence that DBI is expressed in stem cells in all neurogenic niches of the postnatal brain. Focusing on the hippocampal subgranular zone (SGZ) and employing multiple genetic manipulations in vivo, we demonstrate that DBI regulates the balance between preserving the stem cell pool and neurogenesis. Specifically, DBI dampens GABA activity in stem cells, thereby sustaining the proproliferative effect of physical exercise and enriched environment. Our data lend credence to the notion that the modulatory effect of DBI constitutes a general mechanism that regulates postnatal neurogenesis.
Department of Clinical Neurobiology at the German Cancer Research Center (DKFZ) and the Medical Faculty of the Heidelberg University, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Ionut
I
Dumitru
Department of Clinical Neurobiology at the German Cancer Research Center (DKFZ) and the Medical Faculty of the Heidelberg University, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Angela
A
Neitz
Department of Clinical Neurobiology at the German Cancer Research Center (DKFZ) and the Medical Faculty of the Heidelberg University, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. Electronic address: j.alfonso@dkfz-heidelberg.de.
Julieta
J
Alfonso
Department of Clinical Neurobiology at the German Cancer Research Center (DKFZ) and the Medical Faculty of the Heidelberg University, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. Electronic address: h.monyer@dkfz-heidelberg.de.
Hannah
H
Monyer
D000818:Animals; D049109:Cell Proliferation / Q000235:genetics*; D026261:Diazepam Binding Inhibitor / Q000235:genetics* / Q000378:metabolism; D004777:Environment; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry; D008253:Macaca mulatta; D051379:Mice; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics*; D018408:Patch-Clamp Techniques; D011963:Receptors, GABA-A / Q000378:metabolism
D026261:Diazepam Binding Inhibitor; D011963:Receptors, GABA-A
DBI knockout; GABA(A) receptor; ODN; adult neurogenesis; enriched environment; gamma2 F77I; hippocampus; neural proliferation; stem cells