Antibody-mediated stabilization of NRG1 induces behavioral and electrophysiological alterations in adult mice

Scientific Reports
Sara L DominguezErica L Jackson

Abstract

Neuregulin 1 (NRG1) is required for development of the central and peripheral nervous system and regulates neurotransmission in the adult. NRG1 and the gene encoding its receptor, ERBB4, are risk genes for schizophrenia, although how alterations in these genes disrupt their function has not been fully established. Studies of knockout and transgenic mice have yielded conflicting results, with both gain and loss of function resulting in similar behavioral and electrophysiological phenotypes. Here, we used high affinity antibodies to NRG1 and ErbB4 to perturb the function of the endogenous proteins in adult mice. Treatment with NRG1 antibodies that block receptor binding caused behavioral alterations associated with schizophrenia, including, hyper-locomotion and impaired pre-pulse inhibition of startle (PPI). Electrophysiological analysis of brain slices from anti-NRG1 treated mice revealed reduced synaptic transmission and enhanced paired-pulse facilitation. In contrast, mice treated with more potent ErbB4 function blocking antibodies did not display behavioral alterations, suggesting a receptor independent mechanism of the anti-NRG1-induced phenotypes. We demonstrate that anti-NRG1 causes accumulation of the full-length transmem...Continue Reading

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Citations

Dec 30, 2018·Molecular Ecology·Laurence FloriMathieu Gautier
Sep 1, 2021·Neurobiology of Disease·Robert BrendzaBrad A Friedman

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Methods Mentioned

BETA
phage display
ELISA
transfection
FACS
transgenic
Surface Plasmon Resonance
biosensor
chips
enzyme-linked immonosorbent assay

Software Mentioned

GraphPad Prism
Biacore
BIAcore Evaluation T200

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