Genetic fate mapping of type-1 stem cell-dependent increase in newborn hippocampal neurons after electroconvulsive seizures.
Electroconvulsive therapy (ECT) is a uniquely effective treatment for major depressive disorder. An increase in hippocampal neurogenesis is implicated in the recovery from depression. We used an inducible genetic mouse model in which only GFAP-expressing stem-like cells (type-1 cells) and their progeny are selectively labeled with the reporter protein β-galactosidase to track the process of neurogenesis in the dentate gyrus over 3 months following electroconvulsive seizures (ECS), the mouse equivalent of ECT. All ECS protocols tested induced a transient increase in type-1 cell divisions. While this led to an expansion of the type-1 cell pool after high-frequency ECS sessions for 5 consecutive days (5-ECS), asymmetric divisions drove neurogenesis by giving rise to Doublecortin (DCX)-expressing neuroblasts that matured into NeuN+ neurons. Significantly, the increase in newly generated DCX+ and NeuN+ cells after 5-ECS could be traced back to proliferating type-1 cells. Low-frequency continuation ECS (c-ECS) consisting of five single ECS sessions administered every 2 weeks resulted in a similar increase in newborn neurons as the high-frequency 5-ECS protocol. Moreover, the combination of 5-ECS and c-ECS led to a further significant increase in newborn neurons, suggesting a cellular mechanism responsible for the propitious effects of high-frequency ECT followed by continuation ECT in severely depressed patients. The ability of high- and low-frequency ECS to induce normally quiescent type-1 cells to proliferate and generate new neurons sets it apart from other antidepressant treatments and may underlie the superior clinical efficacy of ECT.
['Weber|Tillmann|T|', 'Baier|Vera|V|', 'Lentz|Katharina|K|', 'Herrmann|Elke|E|', 'Krumm|Bertram|B|', 'Sartorius|Alexander|A|', 'Kronenberg|Golo|G|', 'Bartsch|Dusan|D|']
D000818:Animals D000831:Animals, Newborn D002874:Chromosome Mapping D004195:Disease Models, Animal D000089622:Doublecortin Domain Proteins D000089662:Doublecortin Protein D004318:Doxycycline D004597:Electroshock D005786:Gene Expression Regulation D005904:Glial Fibrillary Acidic Protein D049452:Green Fluorescent Proteins D006624:Hippocampus D051379:Mice D008822:Mice, Transgenic D008869:Microtubule-Associated Proteins D009154:Mutation D009474:Neurons D009479:Neuropeptides D010751:Phosphopyruvate Hydratase D022661:RNA, Untranslated D012640:Seizures D013234:Stem Cells
genetic fate mapping electroconvulsive therapy adult neurogenesis cell proliferation hippocampus