Hyperactivity is a Core Endophenotype of Elevated Neuregulin-1 Signaling in Embryonic Glutamatergic Networks
2021 | journal article. A publication with affiliation to the University of Göttingen.
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Hyperactivity is a Core Endophenotype of Elevated Neuregulin-1 Signaling in Embryonic Glutamatergic Networks
Götze, T.; Soto-Bernardini, M. C.; Zhang, M.; Mießner, H.; Linhoff, L.; Brzózka, M. M & Velanac, V. et al. (2021)
Schizophrenia Bulletin,. DOI: https://doi.org/10.1093/schbul/sbab027
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Details
- Authors
- Götze, Tilmann; Soto-Bernardini, Maria Clara; Zhang, Mingyue; Mießner, Hendrik; Linhoff, Lisa; Brzózka, Magdalena M; Velanac, Viktorija; Dullin, Christian; Ramos-Gomes, Fernanda; Schwab, Markus H
- Abstract
- Abstract The neuregulin 1 (NRG1) ErbB4 module is at the core of an “at risk” signaling pathway in schizophrenia. Several human studies suggest hyperstimulation of NRG1-ErbB4 signaling as a plausible pathomechanism; however, little is known about the significance of stage-, brain area-, or neural cell type-specific NRG1-ErbB4 hyperactivity for disease-relevant brain endophenotypes. To address these spatiotemporal aspects, we generated transgenic mice for Cre recombinase-mediated overexpression of cystein-rich domain (CRD) NRG1, the most prominent NRG1 isoform in the brain. A comparison of “brain-wide” vs cell type-specific CRD-NRG1 overexpressing mice revealed that pathogenic CRD-NRG1 signals for ventricular enlargement and neuroinflammation originate outside glutamatergic neurons and suggests a subcortical function of CRD-NRG1 in the control of body weight. Embryonic onset of CRD-NRG1 in glutamatergic cortical networks resulted in reduced inhibitory neurotransmission and locomotor hyperactivity. Our findings identify ventricular enlargement and locomotor hyperactivity, 2 main endophenotypes of schizophrenia, as specific consequences of spatiotemporally distinct expression profiles of hyperactivated CRD-NRG1 signaling.
- Issue Date
- 2021
- Journal
- Schizophrenia Bulletin
- ISSN
- 0586-7614
- eISSN
- 1745-1701
- Language
- English