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Creator |
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Creator |
ext-162f67acdb7e7e027165a660e49aca6e |
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Creator |
ext-2526ac82cac2ad9aef069c2d8c900f31 |
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Creator |
ext-3dccd7c7eb0d0d0afcbe0dcb7147e613 |
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Creator |
ext-4797c9b77796c8024f1246a15c391205 |
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Creator |
ext-61670e257fd902fde0d2109c424d8d3d |
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Creator |
ext-79732baa42ebbb052eb27c9d1460f2b9 |
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Creator |
ext-912a26248da62967a8f17d6698a2049b |
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Creator |
ext-adacbaef6a0c49dce05dd47ec604897d |
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Creator |
ext-ca520957ef602d3134d80a481cb69f18 |
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Creator |
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Creator |
ext-e646f54e2bf55b371e0bf594a87b0c2b |
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Creator |
ext-fe87be763e6360181ca60abafd8ed387 |
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Date |
2011-09-21 |
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Is Part Of |
repository |
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Is Part Of |
p02706474 |
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abstract |
Childhood traumatic events hamper the development of the hippocampus and impair declarative
memory in susceptible individuals. Persistent elevations of hippocampal corticotropin-releasing
factor (CRF), acting through CRF receptor 1 (CRF<sub>1</sub>), in experimental models
of early-life stress have suggested a role for this endogenous stress hormone in the
resulting structural modifications and cognitive dysfunction. However, direct testing
of this possibility has been difficult. In the current study, we subjected conditional
forebrain CRF<sub>1</sub> knock-out (CRF<sub>1</sub>-CKO) mice to an impoverished
postnatal environment and examined the role of forebrain CRF<sub>1</sub> in the long-lasting
effects of early-life stress on learning and memory. Early-life stress impaired spatial
learning and memory in wild-type mice, and postnatal forebrain CRF overexpression
reproduced these deleterious effects. Cognitive deficits in stressed wild-type mice
were associated with disrupted long-term potentiation (LTP) and a reduced number of
dendritic spines in area CA3 but not in CA1. Forebrain CRF<sub>1</sub> deficiency
restored cognitive function, LTP and spine density in area CA3, and augmented CA1
LTP and spine density in stressed mice. In addition, early-life stress differentially
regulated the amount of hippocampal excitatory and inhibitory synapses in wild-type
and CRF<sub>1</sub>-CKO mice, accompanied by alterations in the neurexin-neuroligin
complex. These data suggest that the functional, structural and molecular changes
evoked by early-life stress are at least partly dependent on persistent forebrain
CRF<sub>1</sub> signaling, providing a molecular target for the prevention of cognitive
deficits in adults with a history of early-life adversity. |
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authorList |
authors |
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issue |
38 |
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status |
peerReviewed |
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uri |
http://data.open.ac.uk/oro/document/32449 |
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uri |
http://data.open.ac.uk/oro/document/32451 |
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uri |
http://data.open.ac.uk/oro/document/32452 |
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uri |
http://data.open.ac.uk/oro/document/32466 |
| 29644 |
volume |
31 |
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type |
AcademicArticle |
| 29644 |
type |
Article |
| 29644 |
label |
Wang, Xiao-Dong; Rammes, Gerhard; Kraev, Igor ; Wolf, Miriam; Liebl, Claudia; Scharf,
Sebastian. H.; Rice, Courtney. J.; Wurst, Wolfgang; Holsboer, Florian; Deussing, Jan.
M.; Baram, Tallie. Z.; Stewart, Michael. G. ; Muller, Marianne. B. and Schmidt, Mathias.
V. (2011). Forebrain CRF1 modulates early-life stress-programmed cognitive deficits.
Journal of Neuroscience, 31(38) pp. 13625–13634. |
| 29644 |
label |
Wang, Xiao-Dong; Rammes, Gerhard; Kraev, Igor ; Wolf, Miriam; Liebl, Claudia; Scharf,
Sebastian. H.; Rice, Courtney. J.; Wurst, Wolfgang; Holsboer, Florian; Deussing, Jan.
M.; Baram, Tallie. Z.; Stewart, Michael. G. ; Muller, Marianne. B. and Schmidt, Mathias.
V. (2011). Forebrain CRF1 modulates early-life stress-programmed cognitive deficits.
Journal of Neuroscience, 31(38) pp. 13625–13634. |
| 29644 |
sameAs |
JNEUROSCI.2259-11.2011 |
| 29644 |
Title |
Forebrain CRF<sub>1</sub> modulates early-life stress-programmed cognitive deficits |
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in dataset |
oro |