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Gadd45b Mediates Electroconvulsive Shock Induced Proliferation of Hippocampal Neural Stem Cells.

ABSTRACT: Electroconvulsive shock (ECS), also known as an electroconvulsive therapy (ECT), is an effective and safe treatment for neuropsychiatric disorders including pharmacoresistant major depressive disorder. Previous research in animal models suggests ECS efficacy is achieved by Gadd45b-mediated increases in adult hippocampal neurogenesis.The present study aims to delineate the role of Gadd45b in mediating proliferation of neural stem cell types including quiescent radial glia-like (RGL) and amplifying non-radial glia-like (non-RGL) neural precursors following ECS.RGL and non-RGL neural stem cell populations defined by co-localization of MCM2+ and nestin+ cells and morphologically by the presence of radial processes were stereologically analyzed.ECS increased hippocampal density of both quiescent RGLs and amplifying non-RGLs.Gadd45b mediates the action of ECS-induced proliferation through activation of quiescent neural stem cells.

SUBMITTER: Jun H

PROVIDER: S-EPMC4656097 | biostudies-literature | 2015 Nov-Dec

REPOSITORIES: biostudies-literature

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Gadd45b Mediates Electroconvulsive Shock Induced Proliferation of Hippocampal Neural Stem Cells.

Jun Heechul H Mohammed Qasim Hussaini Syed S Cho Chang Hoon CH Welby John J Jang Mi-Hyeon MH

Brain stimulation 20150728 6

<h4>Background</h4>Electroconvulsive shock (ECS), also known as an electroconvulsive therapy (ECT), is an effective and safe treatment for neuropsychiatric disorders including pharmacoresistant major depressive disorder. Previous research in animal models suggests ECS efficacy is achieved by Gadd45b-mediated increases in adult hippocampal neurogenesis.<h4>Objective/hypothesis</h4>The present study aims to delineate the role of Gadd45b in mediating proliferation of neural stem cell types includin ...[more]

PMID: 26281755

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Project description:Macroautophagy/autophagy is generally regarded as a cytoprotective mechanism, and it remains a matter of controversy whether autophagy can cause cell death in mammals. Here, we show that chronic restraint stress suppresses adult hippocampal neurogenesis in mice by inducing autophagic cell death (ACD) of hippocampal neural stem cells (NSCs). We generated NSC-specific, inducible Atg7 conditional knockout mice and found that they had an intact number of NSCs and neurogenesis level under chronic restraint stress and were resilient to stress- or corticosterone-induced cognitive and mood deficits. Corticosterone treatment of adult hippocampal NSC cultures induced ACD via SGK3 (serum/glucocorticoid regulated kinase 3) without signs of apoptosis. Our results demonstrate that ACD is biologically important in a mammalian system in vivo and would be an attractive target for therapeutic intervention for psychological stress-induced disorders.Abbreviations: AAV: adeno-associated virus; ACD: autophagic cell death; ACTB: actin, beta; Atg: autophagy-related; ASCL1/MASH1: achaete-scute family bHLH transcription factor 1; BafA1: bafilomycin A1; BrdU: Bromodeoxyuridine/5-bromo-2'-deoxyuridine; CASP3: caspase 3; cKO: conditional knockout; CLEM: correlative light and electron microscopy; CORT: corticosterone; CRS: chronic restraint stress; DAB: 3,3'-diaminobenzidine; DCX: doublecortin; DG: dentate gyrus; GC: glucocorticoid; GFAP: glial fibrillary acidic protein; HCN: hippocampal neural stem; i.p.: intraperitoneal; MAP1LC3B: microtubule-associated protein 1 light chain 3 beta; MKI67/Ki67: antigen identified by monoclonal antibody Ki 67; MWM: Morris water maze; Nec-1: necrostatin-1; NES: nestin; NR3C1/GR: nuclear receptor subfamily 3, group C, member 1; NSC: neural stem cell; PCD: programmed cell death; PFA: paraformaldehyde; PX: Phox homology; PtdIns3P: phosphatidylinositol-3-phosphate; RBFOX3/NeuN: RNA binding protein, fox-1 homolog (C. elegans) 3; SGK: serum/glucocorticoid-regulated kinases; SGZ: subgranular zone; SOX2: SRY (sex determining region Y)-box 2; SQSTM1: sequestosome 1; STS: staurosporine; TAM: tamoxifen; Ulk1: unc-51 like kinase 1; TUNEL: terminal deoxynucleotidyl transferase dUTP nick end labeling; VIM: vimentin; WT: wild type; ZFYVE1: zinc finger, FYVE domain containing 1; Z-VAD/Z-VAD-FMK: pan-caspase inhibitor.

Dataset Information

Gadd45b Mediates Electroconvulsive Shock Induced Proliferation of Hippocampal Neural Stem Cells.

Publications

Gadd45b Mediates Electroconvulsive Shock Induced Proliferation of Hippocampal Neural Stem Cells.

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