Rapid spinogenesis of pyramidal neurons induced by activation of glucocorticoid receptors in adult male rat hippocampus.
Modulation of hippocampal synaptic plasticity by glucocorticoids has been attracting much attention, due to its importance in stress responses. Dendritic spines are essential for memory storage processes. Here, we investigated the effect of dexamethasone (DEX), a specific agonist of glucocorticoid receptor (GR), on density and morphology of dendritic spines in adult male rat hippocampus by imaging of Lucifer Yellow-injected spines in slices. The application of 100 nM DEX (stressful high concentration) induced rapid modulation of the density and morphology of dendritic spines in CA1 pyramidal neurons within 1h. The total spine density increased from 0.88 spines/microm (control) to 1.36 spines/microm (DEX-treated). DEX significantly increased the density of thin and mushroom type spines, however only a slight increase was observed for stubby and filopodium type spines. Because the presence of 10 microM cycloheximide, an inhibitor of protein synthesis, did not suppress the DEX effect, these responses are probably non-genomic. Western immunoblot analysis demonstrated the localization of classical type GR in Triton-insoluble synaptosomal fractions (enriched in postsynaptic membranes) from hippocampal slices, suggesting a possible action site of DEX at spines.
Komatsuzaki
Yoshimasa
Y
School of Science and Technology, Meiji University, 1-1-1 Higasimita, Tama, Kawasaki, Kanagawa 214, Japan.
Murakami
Gen
G
Tsurugizawa
Tomokazu
T
Mukai
Hideo
H
Tanabe
Nobuaki
N
Mitsuhashi
Kenji
K
Kawata
Mitsuhiro
M
Kimoto
Tetsuya
T
Ooishi
Yuuki
Y
Kawato
Suguru
S
D000818:Animals; D049108:Cell Enlargement / Q000187:drug effects; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure; D003907:Dexamethasone / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000819:agonists* / Q000378:metabolism*
D011965:Receptors, Glucocorticoid; D003907:Dexamethasone