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Neuropathologic Implication of Peripheral Neuregulin-1 and EGF Signals in Dopaminergic Dysfunction and Behavioral Deficits Relevant to Schizophrenia: Their Target Cells and Time Window
Neuregulin-1 and epidermal growth factor (EGF) are implicated in the pathogenesis of schizophrenia. To test the developmental hypothesis for schizophrenia, we administered these factors to rodent pups, juveniles, and adults and characterized neurobiological and behavioral consequences. These factors...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2014
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4052624/ https://www.ncbi.nlm.nih.gov/pubmed/24949465 http://dx.doi.org/10.1155/2014/697935 |
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author | Nawa, Hiroyuki Sotoyama, Hidekazu Iwakura, Yuriko Takei, Nobuyuki Namba, Hisaaki |
author_facet | Nawa, Hiroyuki Sotoyama, Hidekazu Iwakura, Yuriko Takei, Nobuyuki Namba, Hisaaki |
author_sort | Nawa, Hiroyuki |
collection | PubMed |
description | Neuregulin-1 and epidermal growth factor (EGF) are implicated in the pathogenesis of schizophrenia. To test the developmental hypothesis for schizophrenia, we administered these factors to rodent pups, juveniles, and adults and characterized neurobiological and behavioral consequences. These factors were also provided from their transgenes or infused into the adult brain. Here we summarize previous results from these experiments and discuss those from neuropathological aspects. In the neonatal stage but not the juvenile and adult stages, subcutaneously injected factors penetrated the blood-brain barrier and acted on brain neurons, which later resulted in persistent behavioral and dopaminergic impairments associated with schizophrenia. Neonatally EGF-treated animals exhibited persistent hyperdopaminergic abnormalities in the nigro-pallido-striatal system while neuregulin-1 treatment resulted in dopaminergic deficits in the corticolimbic dopamine system. Effects on GABAergic and glutamatergic systems were transient or limited. Even in the adult stage, intracerebral administration and transgenic expression of these factors produced similar but not identical behavioral impairments, although the effects of intracerebral administration were reversible. These findings suggest that dopaminergic development is highly vulnerable to circulating ErbB ligands in the pre- and perinatal stages. Once maldevelopment of the dopaminergic system is established during early development, dopamine-associating behavioral deficits become irreversible and manifest at postpubertal stages. |
format | Online Article Text |
id | pubmed-4052624 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-40526242014-06-19 Neuropathologic Implication of Peripheral Neuregulin-1 and EGF Signals in Dopaminergic Dysfunction and Behavioral Deficits Relevant to Schizophrenia: Their Target Cells and Time Window Nawa, Hiroyuki Sotoyama, Hidekazu Iwakura, Yuriko Takei, Nobuyuki Namba, Hisaaki Biomed Res Int Review Article Neuregulin-1 and epidermal growth factor (EGF) are implicated in the pathogenesis of schizophrenia. To test the developmental hypothesis for schizophrenia, we administered these factors to rodent pups, juveniles, and adults and characterized neurobiological and behavioral consequences. These factors were also provided from their transgenes or infused into the adult brain. Here we summarize previous results from these experiments and discuss those from neuropathological aspects. In the neonatal stage but not the juvenile and adult stages, subcutaneously injected factors penetrated the blood-brain barrier and acted on brain neurons, which later resulted in persistent behavioral and dopaminergic impairments associated with schizophrenia. Neonatally EGF-treated animals exhibited persistent hyperdopaminergic abnormalities in the nigro-pallido-striatal system while neuregulin-1 treatment resulted in dopaminergic deficits in the corticolimbic dopamine system. Effects on GABAergic and glutamatergic systems were transient or limited. Even in the adult stage, intracerebral administration and transgenic expression of these factors produced similar but not identical behavioral impairments, although the effects of intracerebral administration were reversible. These findings suggest that dopaminergic development is highly vulnerable to circulating ErbB ligands in the pre- and perinatal stages. Once maldevelopment of the dopaminergic system is established during early development, dopamine-associating behavioral deficits become irreversible and manifest at postpubertal stages. Hindawi Publishing Corporation 2014 2014-05-13 /pmc/articles/PMC4052624/ /pubmed/24949465 http://dx.doi.org/10.1155/2014/697935 Text en Copyright © 2014 Hiroyuki Nawa et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Review Article Nawa, Hiroyuki Sotoyama, Hidekazu Iwakura, Yuriko Takei, Nobuyuki Namba, Hisaaki Neuropathologic Implication of Peripheral Neuregulin-1 and EGF Signals in Dopaminergic Dysfunction and Behavioral Deficits Relevant to Schizophrenia: Their Target Cells and Time Window |
title | Neuropathologic Implication of Peripheral Neuregulin-1 and EGF Signals in Dopaminergic Dysfunction and Behavioral Deficits Relevant to Schizophrenia: Their Target Cells and Time Window |
title_full | Neuropathologic Implication of Peripheral Neuregulin-1 and EGF Signals in Dopaminergic Dysfunction and Behavioral Deficits Relevant to Schizophrenia: Their Target Cells and Time Window |
title_fullStr | Neuropathologic Implication of Peripheral Neuregulin-1 and EGF Signals in Dopaminergic Dysfunction and Behavioral Deficits Relevant to Schizophrenia: Their Target Cells and Time Window |
title_full_unstemmed | Neuropathologic Implication of Peripheral Neuregulin-1 and EGF Signals in Dopaminergic Dysfunction and Behavioral Deficits Relevant to Schizophrenia: Their Target Cells and Time Window |
title_short | Neuropathologic Implication of Peripheral Neuregulin-1 and EGF Signals in Dopaminergic Dysfunction and Behavioral Deficits Relevant to Schizophrenia: Their Target Cells and Time Window |
title_sort | neuropathologic implication of peripheral neuregulin-1 and egf signals in dopaminergic dysfunction and behavioral deficits relevant to schizophrenia: their target cells and time window |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4052624/ https://www.ncbi.nlm.nih.gov/pubmed/24949465 http://dx.doi.org/10.1155/2014/697935 |
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