TY - JOUR
T1 - Reversal of behavioral deficits and synaptic dysfunction in mice overexpressing neuregulin 1
AU - Yin, Dong Min
AU - Chen, Yong Jun
AU - Lu, Yi Sheng
AU - Bean, Jonathan C.
AU - Sathyamurthy, Anupama
AU - Shen, Chengyong
AU - Liu, Xihui
AU - Lin, Thiri W.
AU - Smith, Clifford A.
AU - Xiong, Wen Cheng
AU - Mei, Lin
PY - 2013/5/22
Y1 - 2013/5/22
N2 - Neuregulin 1 (. Nrg1) is a susceptibility gene of schizophrenia, a disabling mental illness that affects 1% of the general population. Here, we show that cto. Nrg1 mice, which mimic high levels of NRG1 observed in forebrain regions of schizophrenic patients, exhibit behavioral deficits and hypofunction of glutamatergic and GABAergic pathways. Intriguingly, these deficits were diminished when NRG1 expression returned to normal in adult mice, suggesting that damage which occurred during development is recoverable. Conversely, increase of NRG1 in adulthood was sufficient to cause glutamatergic impairment and behavioral deficits. We found that the glutamatergic impairment by NRG1 overexpression required LIM domain kinase 1 (LIMK1), which was activated in mutant mice, identifying a pathological mechanism. These observations demonstrate that synaptic dysfunction and behavioral deficits in cto. Nrg1 mice require continuous NRG1 abnormality in adulthood, suggesting that relevant schizophrenia may benefit from therapeutic intervention to restore NRG1 signaling
AB - Neuregulin 1 (. Nrg1) is a susceptibility gene of schizophrenia, a disabling mental illness that affects 1% of the general population. Here, we show that cto. Nrg1 mice, which mimic high levels of NRG1 observed in forebrain regions of schizophrenic patients, exhibit behavioral deficits and hypofunction of glutamatergic and GABAergic pathways. Intriguingly, these deficits were diminished when NRG1 expression returned to normal in adult mice, suggesting that damage which occurred during development is recoverable. Conversely, increase of NRG1 in adulthood was sufficient to cause glutamatergic impairment and behavioral deficits. We found that the glutamatergic impairment by NRG1 overexpression required LIM domain kinase 1 (LIMK1), which was activated in mutant mice, identifying a pathological mechanism. These observations demonstrate that synaptic dysfunction and behavioral deficits in cto. Nrg1 mice require continuous NRG1 abnormality in adulthood, suggesting that relevant schizophrenia may benefit from therapeutic intervention to restore NRG1 signaling
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U2 - 10.1016/j.neuron.2013.03.028
DO - 10.1016/j.neuron.2013.03.028
M3 - Article
C2 - 23719163
AN - SCOPUS:84878445594
VL - 78
SP - 644
EP - 657
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 4
ER -