Protein phosphatase 1-dependent bidirectional synaptic plasticity controls ischemic recovery in the adult brain
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Protein phosphatase 1-dependent bidirectional synaptic plasticity controls ischemic recovery in the adult brain. / Hédou, Gaël F; Koshibu, Kyoko; Farinelli, Mélissa; Kilic, Ertugrul; Gee, Christine E; Kilic, Ulkan; Baumgärtel, Karsten; Hermann, Dirk M; Mansuy, Isabelle M.
In: J NEUROSCI, Vol. 28, No. 1, 02.01.2008, p. 154-62.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Protein phosphatase 1-dependent bidirectional synaptic plasticity controls ischemic recovery in the adult brain
AU - Hédou, Gaël F
AU - Koshibu, Kyoko
AU - Farinelli, Mélissa
AU - Kilic, Ertugrul
AU - Gee, Christine E
AU - Kilic, Ulkan
AU - Baumgärtel, Karsten
AU - Hermann, Dirk M
AU - Mansuy, Isabelle M
PY - 2008/1/2
Y1 - 2008/1/2
N2 - Protein kinases and phosphatases can alter the impact of excitotoxicity resulting from ischemia by concurrently modulating apoptotic/survival pathways. Here, we show that protein phosphatase 1 (PP1), known to constrain neuronal signaling and synaptic strength (Mansuy et al., 1998; Morishita et al., 2001), critically regulates neuroprotective pathways in the adult brain. When PP1 is inhibited pharmacologically or genetically, recovery from oxygen/glucose deprivation (OGD) in vitro, or ischemia in vivo is impaired. Furthermore, in vitro, inducing LTP shortly before OGD similarly impairs recovery, an effect that correlates with strong PP1 inhibition. Conversely, inducing LTD before OGD elicits full recovery by preserving PP1 activity, an effect that is abolished by PP1 inhibition. The mechanisms of action of PP1 appear to be coupled with several components of apoptotic pathways, in particular ERK1/2 (extracellular signal-regulated kinase 1/2) whose activation is increased by PP1 inhibition both in vitro and in vivo. Together, these results reveal that the mechanisms of recovery in the adult brain critically involve PP1, and highlight a novel physiological function for long-term potentiation and long-term depression in the control of brain damage and repair.
AB - Protein kinases and phosphatases can alter the impact of excitotoxicity resulting from ischemia by concurrently modulating apoptotic/survival pathways. Here, we show that protein phosphatase 1 (PP1), known to constrain neuronal signaling and synaptic strength (Mansuy et al., 1998; Morishita et al., 2001), critically regulates neuroprotective pathways in the adult brain. When PP1 is inhibited pharmacologically or genetically, recovery from oxygen/glucose deprivation (OGD) in vitro, or ischemia in vivo is impaired. Furthermore, in vitro, inducing LTP shortly before OGD similarly impairs recovery, an effect that correlates with strong PP1 inhibition. Conversely, inducing LTD before OGD elicits full recovery by preserving PP1 activity, an effect that is abolished by PP1 inhibition. The mechanisms of action of PP1 appear to be coupled with several components of apoptotic pathways, in particular ERK1/2 (extracellular signal-regulated kinase 1/2) whose activation is increased by PP1 inhibition both in vitro and in vivo. Together, these results reveal that the mechanisms of recovery in the adult brain critically involve PP1, and highlight a novel physiological function for long-term potentiation and long-term depression in the control of brain damage and repair.
KW - Animals
KW - Animals, Genetically Modified
KW - Anoxia
KW - Brain Ischemia
KW - Calcium-Calmodulin-Dependent Protein Kinase Type 2
KW - Disease Models, Animal
KW - Dose-Response Relationship, Drug
KW - Dose-Response Relationship, Radiation
KW - Doxycycline
KW - Electric Stimulation
KW - Enzyme Inhibitors
KW - Gene Expression Regulation
KW - Glucose
KW - Hippocampus
KW - In Vitro Techniques
KW - Long-Term Synaptic Depression
KW - Mice
KW - Mice, Inbred C57BL
KW - Neuronal Plasticity
KW - Protein Phosphatase 1
KW - Proteins
KW - Pyrans
KW - Recovery of Function
KW - Spiro Compounds
U2 - 10.1523/JNEUROSCI.4109-07.2008
DO - 10.1523/JNEUROSCI.4109-07.2008
M3 - SCORING: Journal article
C2 - 18171933
VL - 28
SP - 154
EP - 162
JO - J NEUROSCI
JF - J NEUROSCI
SN - 0270-6474
IS - 1
ER -