title: Ablation of hippocampal neurogenesis in mice impairs the response to stress during the dark cycle.
abstract: The functional role of adult neurogenesis in the hippocampus remains the subject of intense speculation. One recent hypothesis is that adult-born neurons contribute to the endocrine and behavioural outputs of the stress response. Here we show a genetic model system to ablate neurogenesis by inducibly deleting Tbr2 gene function specifically in the hippocampus and corroborate our findings in a radiation-based model of neurogenesis deprivation. We found that mice with ablation of new neurons in the dentate gyrus exhibit reduced anxiety during the dark cycle. After restraint stress, corticosterone levels in neurogenesis-deficient mice decreased more quickly than controls and were more sensitive to suppression by dexamethasone. Furthermore, glucocorticoid receptor target genes and neuronal activity markers showed reduced expression after stress in neurogenesis-deficient mice. These findings suggest that newborn neurons in the hippocampus are involved in sensing and eliciting an appropriate response to stress.
authors.affiliation: Department and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan 33302, Taiwan.
authors.forename: Cheng-Yu
authors.initials: CY
authors.lastname: Tsai
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Ching-Yen
authors.initials: CY
authors.lastname: Tsai
authors.affiliation: Renal Department, University Medical Centre, Centre for Clinical Research, Freiburg 79106, Germany.|Institute of Experimental and Clinical Pharmacology and Toxicology, Albert-Ludwigs-University, Freiburg 79102, Germany.|BIOSS Centre of Biological Signalling Studies, Albert-Ludwigs-University, Freiburg 79104, Germany.
authors.forename: Sebastian J
authors.initials: SJ
authors.lastname: Arnold
authors.affiliation: Department and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan 33302, Taiwan.|Healthy Aging Research Center, Chang Gung University, Tao-Yuan 33902, Taiwan.
authors.forename: Guo-Jen
authors.initials: GJ
authors.lastname: Huang
mesh_terms: D000818:Animals; D001007:Anxiety; D003345:Corticosterone / Q000097:blood; D003624:Darkness; D018891:Dentate Gyrus / Q000502:physiology*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055495:Neurogenesis; D013315:Stress, Psychological / Q000097:blood / Q000503:physiopathology*; D020825:T-Box Domain Proteins / Q000235:genetics
chemical_list: C491198:Eomes protein, mouse; D020825:T-Box Domain Proteins; D003345:Corticosterone