Schizophrenia Animal Modeling with Epidermal Growth Factor and Its Homologs: Their Connections to the Inflammatory Pathway and the Dopamine System.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101596414 Publication Model: Electronic Cited Medium: Internet ISSN: 2218-273X (Electronic) Linking ISSN: 2218273X NLM ISO Abbreviation: Biomolecules Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, 2011-

Schizophrenia* ; COVID-19*; Mice ; Pregnancy ; Female ; Rats ; Animals ; Epidermal Growth Factor/metabolism ; Dopamine/metabolism ; ErbB Receptors/metabolism ; Disease Models, Animal ; Mice, Transgenic

Epidermal growth factor (EGF) and its homologs, such as neuregulins, bind to ErbB (Her) receptor kinases and regulate glial differentiation and dopaminergic/GABAergic maturation in the brain and are therefore implicated in schizophrenia neuropathology involving these cell abnormalities. In this review, we summarize the biological activities of the EGF family and its neuropathologic association with schizophrenia, mainly overviewing our previous model studies and the related articles. Transgenic mice as well as the rat/monkey models established by perinatal challenges of EGF or its homologs consistently exhibit various behavioral endophenotypes relevant to schizophrenia. In particular, post-pubertal elevation in baseline dopaminergic activity may illustrate the abnormal behaviors relevant to positive and negative symptoms as well as to the timing of this behavioral onset. With the given molecular interaction and transactivation of ErbB receptor kinases with Toll-like receptors (TLRs), EGF/ErbB signals are recruited by viral infection and inflammatory diseases such as COVID-19-mediated pneumonia and poxvirus-mediated fibroma and implicated in the immune-inflammatory hypothesis of schizophrenia. Finally, we also discuss the interaction of clozapine with ErbB receptor kinases as well as new antipsychotic development targeting these receptors.

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18H05429, 18H05428, 21K18242, 22H02728 Japan Society for the Promotion of Science; 22H02728 JSPS; 21K18242 JSPS; 22H02728 JSPS

Keywords: ErbB kinase; TLR; cytokine; inflammation; negative symptom; neuregulin; schizophrenia

62229-50-9 (Epidermal Growth Factor)
VTD58H1Z2X (Dopamine)
EC 2.7.10.1 (ErbB Receptors)

Date Created: 20230225 Date Completed: 20230228 Latest Revision: 20230310

20231215

PMC9953688

10.3390/biom13020372

36830741