Reversal of behavioral deficits and synaptic dysfunction in mice overexpressing neuregulin 1

Dong Min Yin, Yong Jun Chen, Yi Sheng Lu, Jonathan C. Bean, Anupama Sathyamurthy, Chengyong Shen, Xihui Liu, Thiri W. Lin, Clifford A. Smith, Wen Cheng Xiong, Lin Mei

Research output: Contribution to journalArticlepeer-review

101 Scopus citations


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

Original languageEnglish (US)
Pages (from-to)644-657
Number of pages14
Issue number4
StatePublished - May 22 2013

ASJC Scopus subject areas

  • Neuroscience(all)


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