TY - JOUR
T1 - Behavioral stress modifies hippocampal synaptic plasticity through corticosterone-induced sustained extracellular signal-regulated kinase/mitogen-activated protein kinase activation
AU - Yang, Chih Hao
AU - Huang, Chiung Chun
AU - Hsu, Kuei Sen
PY - 2004/12/8
Y1 - 2004/12/8
N2 - The induction of hippocampal long-term synaptic plasticity is exquisitely sensitive to behavioral stress, but the underlying mechanisms are still unclear. We report here that hippocampal slices prepared from adult rats that had experienced unpredictable and inescapable restraint tail-shock stress showed marked impairments of long-term potentiation (LTP) in the CA1 region. The same stress promoted the induction of long-term depression (LTD). These effects were prevented when the animals were given the glucocorticoid receptor antagonist 11β,17β-11[4-(dimethylamino)phenyl]-17-hydroxy-17-(1-propynyl) -estra-4-9-dien-3-one before the stress. Immunoblotting analyses revealed that stress induced a profound and prolonged extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK1/2 MAPK) hyperphosphorylation through small GTPase Ras, Raf-1, and MAPK kinase 1/2 (MEK1/2). Furthermore, the stress effects were obviated by the intrahippocampal injection of specific inhibitors of MEK1/2 (U0126), protein kinase C (bisindolylmaleimide I), tyrosine kinase (K252a), and BDNF antisense oligonucleotides. These results suggest that the effects of stress on LTP and LTD originate from the corticosterone-induced sustained activation of ERK1/2-coupled signaling cascades.
AB - The induction of hippocampal long-term synaptic plasticity is exquisitely sensitive to behavioral stress, but the underlying mechanisms are still unclear. We report here that hippocampal slices prepared from adult rats that had experienced unpredictable and inescapable restraint tail-shock stress showed marked impairments of long-term potentiation (LTP) in the CA1 region. The same stress promoted the induction of long-term depression (LTD). These effects were prevented when the animals were given the glucocorticoid receptor antagonist 11β,17β-11[4-(dimethylamino)phenyl]-17-hydroxy-17-(1-propynyl) -estra-4-9-dien-3-one before the stress. Immunoblotting analyses revealed that stress induced a profound and prolonged extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK1/2 MAPK) hyperphosphorylation through small GTPase Ras, Raf-1, and MAPK kinase 1/2 (MEK1/2). Furthermore, the stress effects were obviated by the intrahippocampal injection of specific inhibitors of MEK1/2 (U0126), protein kinase C (bisindolylmaleimide I), tyrosine kinase (K252a), and BDNF antisense oligonucleotides. These results suggest that the effects of stress on LTP and LTD originate from the corticosterone-induced sustained activation of ERK1/2-coupled signaling cascades.
KW - Extracellular signal-related kinase
KW - Glucocorticoid receptor
KW - Hippocampus
KW - Long-term depression
KW - Long-term potentiation
KW - Mitogen-activated protein kinase
KW - Stress
UR - http://www.scopus.com/inward/record.url?scp=10944243551&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=10944243551&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.3968-04.2004
DO - 10.1523/JNEUROSCI.3968-04.2004
M3 - Article
C2 - 15590919
AN - SCOPUS:10944243551
SN - 0270-6474
VL - 24
SP - 11029
EP - 11034
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 49
ER -