title: Increased P27KIP1 protein expression in the dentate gyrus of chronically stressed rats indicates G1 arrest involvement.
abstract: Various chronic stress paradigms decrease new cell proliferation in the hippocampal dentate gyrus, yet the exact underlying mechanism is still unclear. In the first gap (G1) phase of the cell cycle, both stimulatory and inhibitory signals derived from the extracellular environment converge. Corticosteroids, which increase during stress and are well-known anti-mitotics, cause cells in vitro to arrest in the G1 phase. Following 3 weeks of unpredictable stress, we therefore expected a change in protein expression of various important G1 cell cycle regulators in the adult rat subgranular zone. Using quantitative immunocytochemistry, we show that particularly cyclin-dependent kinase inhibitor p27Kip1 expression is significantly increased. In addition, 3 weeks of recovery after stress normalized the numbers of p27Kip1-expressing cells, consistent with the recovered adult cell proliferation in these animals. P27Kip1-positive cells do not overlap with GFAP-staining and only to a limited extent with Ki-67-expressing cells. Numbers of cyclin E- and cyclin D1-expressing cells did not change after chronic stress. These results indicate that chronic stress causes cycling cells in the adult hippocampus to arrest in G1, thereby providing more mechanistic insight in the stress-induced decrease in cell proliferation.
authors.affiliation: Section Neurobiology, Swammerdam Institute for Life Sciences, University of Amsterdam, Kruislaan 320, 1098 SM, PO Box 94084, Amsterdam, The Netherlands. heine@science.uva.nl
authors.forename: V M
authors.initials: VM
authors.lastname: Heine
authors.forename: S
authors.initials: S
authors.lastname: Maslam
authors.forename: M
authors.initials: M
authors.lastname: Joëls
authors.forename: P J
authors.initials: PJ
authors.lastname: Lucassen
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D002452:Cell Count / Q000379:methods; D018797:Cell Cycle Proteins / Q000378:metabolism*; D003080:Cold Temperature / Q000009:adverse effects; D019938:Cyclin D1 / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism*; D016193:G1 Phase / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007103:Immobilization / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D013312:Stress, Physiological / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: C493962:Cdkn1b protein, rat; D018797:Cell Cycle Proteins; D019927:Cyclin E; D005904:Glial Fibrillary Acidic Protein; D019394:Ki-67 Antigen; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27