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Neuregulin 1 signalling modulates mGluR1 function in mesencephalic dopaminergic neurons

Molecular Psychiatry volume 20, pages 959–973 (2015)Cite this article

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Abstract

Neuregulin 1 (NRG1) is a trophic factor that has an essential role in the nervous system by modulating neurodevelopment, neurotransmission and synaptic plasticity. Despite the evidence that NRG1 and its receptors, ErbB tyrosine kinases, are expressed in mesencephalic dopaminergic nuclei and their functional alterations are reported in schizophrenia and Parkinson’s disease, the role of NRG1/ErbB signalling in dopaminergic neurons remains unclear. Here we found that NRG1 selectively increases the metabotropic glutamate receptor 1 (mGluR1)-activated currents by inducing synthesis and trafficking to membrane of functional receptors and stimulates phosphatidylinositol 3-kinase-Akt-mammalian target of rapamycin (PI3K-Akt-mTOR) pathway, which is required for mGluR1 function. Notably, an endogenous NRG1/ErbB tone is necessary to maintain mGluR1 function, by preserving its surface membrane expression in dopaminergic neurons. Consequently, it enables striatal mGluR1-induced dopamine outflow in in vivo conditions. Our results identify a novel role of NRG1 in the dopaminergic neurons, whose functional alteration might contribute to devastating diseases, such as schizophrenia and Parkinson’s disease.

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Acknowledgements

This work has been financed by Grants from the Minister of Health to NBM, Alzheimer’s Association (NIRG-11-204588) to MDA and the Italian Ministry of University and Research (PRIN 2009) to MDA.

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Authors and Affiliations

  1. Department of Experimental Neurosciences, IRCCS Santa Lucia Foundation, Rome, Italy

    A Ledonne, A Nobili, E C Latagliata, V Cavallucci, E Guatteo, S Puglisi-Allegra, M D'Amelio & N B Mercuri

  2. Department of Systems Medicine, University of Rome ‘Tor Vergata’, Rome, Italy

    A Ledonne & N B Mercuri

  3. Department of Psychology and ‘Daniel Bovet’ Center, University of Rome ‘La Sapienza’, Rome, Italy

    S Puglisi-Allegra

  4. Laboratory of Molecular Neurosciences, Medical School University Campus-Biomedico, Rome, Italy

    M D'Amelio

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  1. A Ledonne
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Ledonne, A., Nobili, A., Latagliata, E. et al. Neuregulin 1 signalling modulates mGluR1 function in mesencephalic dopaminergic neurons. Mol Psychiatry 20, 959–973 (2015). https://doi.org/10.1038/mp.2014.109

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