Abstract
Perinatal exposure to epidermal growth factor (EGF) induces various cognitive and behavioral abnormalities after maturation in non-human animals, and is used for animal models of schizophrenia. Patients with schizophrenia often display a reduction of mismatch negativity (MMN), which is a stimulus-change specific event-related brain potential. Do the EGF model animals also exhibit the MMN reduction as schizophrenic patients do? This study addressed this question to verify the pathophysiological validity of this model. Neonatal rats received repeated administration of EGF or saline and were grown until adulthood. Employing the odd-ball paradigm of distinct tone pitches, tone-evoked electroencephalogram (EEG) components were recorded from electrodes on the auditory and frontal cortices of awake rats, referencing an electrode on the frontal sinus. The amplitude of the MMN-like potential was significantly reduced in EGF-treated rats compared with saline-injected control rats. The wavelet analysis of the EEG during a near period of tone stimulation revealed that synchronization of EEG activity, especially with beta and gamma bands, was reduced in EGF-treated rats. Results suggest that animals exposed to EGF during a perinatal period serve as a promising neurodevelopmental model of schizophrenia.
Highlights
Epidermal growth factor (EGF) is a growth factor and an inflammatory cytokine with 53 amino acid residues, and is known to be a structural homologue of neuregulin-1, whose mutation is implicated in schizophrenia[1,2]
Consistent with previous reports[36,38], in EEG recording from an electrode on the frontal cortex (FC), a human-mismatch negativity (MMN)-like negative potential was elicited around 50 ms after the start of deviant tone presentation
EEG recording from the surface electrode of the auditory cortex (AC) revealed that neither event-related potential (ERP) amplitudes nor waveforms to the standard tone differed between groups (EGF vs. control)
Summary
Epidermal growth factor (EGF) is a growth factor and an inflammatory cytokine with 53 amino acid residues, and is known to be a structural homologue of neuregulin-1, whose mutation is implicated in schizophrenia[1,2]. Peripheral administration of EGF or its orthologues (i.e. transforming growth factor alpha, epiregulin) in a neonatal period induces similar cognitive and behavioral abnormalities during the post-pubertal stages in mice, rats and monkeys[3,15,16,17]. Due to this similarity of age at onset between EGF-treated animals and those with schizophrenia, we hypothesized that the animals exposed to EGF or other ErbB1 ligands in the early stages of development may prove to be a useful neurodevelopmental model of schizophrenia[18]. We recorded the MMN-like potential in one of the putative animal models for schizophrenia, which was perinatally EGF-treated rats, and characterized their deficits in MMN-like potential to evaluate validity of this model for schizophrenia
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
