Cargando…

Sex-specific involvement of the Notch–JAG pathway in social recognition

Under the hypothesis that olfactory neural epithelium gene expression profiles may be useful to look for disease-relevant neuronal signatures, we examined microarray gene expression in olfactory neuronal cells and underscored Notch–JAG pathway molecules in association with schizophrenia (SZ). The mi...

Descripción completa

Detalles Bibliográficos
Autores principales: Jaaro-Peled, Hanna, Landek-Salgado, Melissa A., Cascella, Nicola G., Nucifora, Frederick C., Coughlin, Jennifer M., Nestadt, Gerald, Sedlak, Thomas W., Lavoie, Joelle, De Silva, Sarah, Lee, Somin, Tajinda, Katsunori, Hiyama, Hideki, Ishizuka, Koko, Yang, Kun, Sawa, Akira
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8913639/
https://www.ncbi.nlm.nih.gov/pubmed/35273151
http://dx.doi.org/10.1038/s41398-022-01867-4
_version_ 1784667488253902848
author Jaaro-Peled, Hanna
Landek-Salgado, Melissa A.
Cascella, Nicola G.
Nucifora, Frederick C.
Coughlin, Jennifer M.
Nestadt, Gerald
Sedlak, Thomas W.
Lavoie, Joelle
De Silva, Sarah
Lee, Somin
Tajinda, Katsunori
Hiyama, Hideki
Ishizuka, Koko
Yang, Kun
Sawa, Akira
author_facet Jaaro-Peled, Hanna
Landek-Salgado, Melissa A.
Cascella, Nicola G.
Nucifora, Frederick C.
Coughlin, Jennifer M.
Nestadt, Gerald
Sedlak, Thomas W.
Lavoie, Joelle
De Silva, Sarah
Lee, Somin
Tajinda, Katsunori
Hiyama, Hideki
Ishizuka, Koko
Yang, Kun
Sawa, Akira
author_sort Jaaro-Peled, Hanna
collection PubMed
description Under the hypothesis that olfactory neural epithelium gene expression profiles may be useful to look for disease-relevant neuronal signatures, we examined microarray gene expression in olfactory neuronal cells and underscored Notch–JAG pathway molecules in association with schizophrenia (SZ). The microarray profiling study underscored JAG1 as the most promising candidate. Combined with further validation with real-time PCR, downregulation of NOTCH1 was statistically significant. Accordingly, we reverse-translated the significant finding from a surrogate tissue for neurons, and studied the behavioral profile of Notch1(+/−) mice. We found a specific impairment in social novelty recognition, whereas other behaviors, such as sociability, novel object recognition and olfaction of social odors, were normal. This social novelty recognition deficit was male-specific and was rescued by rapamycin treatment. Based on the results from the animal model, we next tested whether patients with psychosis might have male-specific alterations in social cognition in association with the expression of NOTCH1 or JAG1. In our first episode psychosis cohort, we observed a specific correlation between the expression of JAG1 and a face processing measure only in male patients. The expression of JAG1 was not correlated with any other cognitive and symptomatic scales in all subjects. Together, although we acknowledge the pioneering and exploratory nature, the present work that combines both human and animal studies in a reciprocal manner suggests a novel role for the Notch–JAG pathway in a behavioral dimension(s) related to social cognition in psychotic disorders in a male-specific manner.
format Online
Article
Text
id pubmed-8913639
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-89136392022-03-25 Sex-specific involvement of the Notch–JAG pathway in social recognition Jaaro-Peled, Hanna Landek-Salgado, Melissa A. Cascella, Nicola G. Nucifora, Frederick C. Coughlin, Jennifer M. Nestadt, Gerald Sedlak, Thomas W. Lavoie, Joelle De Silva, Sarah Lee, Somin Tajinda, Katsunori Hiyama, Hideki Ishizuka, Koko Yang, Kun Sawa, Akira Transl Psychiatry Article Under the hypothesis that olfactory neural epithelium gene expression profiles may be useful to look for disease-relevant neuronal signatures, we examined microarray gene expression in olfactory neuronal cells and underscored Notch–JAG pathway molecules in association with schizophrenia (SZ). The microarray profiling study underscored JAG1 as the most promising candidate. Combined with further validation with real-time PCR, downregulation of NOTCH1 was statistically significant. Accordingly, we reverse-translated the significant finding from a surrogate tissue for neurons, and studied the behavioral profile of Notch1(+/−) mice. We found a specific impairment in social novelty recognition, whereas other behaviors, such as sociability, novel object recognition and olfaction of social odors, were normal. This social novelty recognition deficit was male-specific and was rescued by rapamycin treatment. Based on the results from the animal model, we next tested whether patients with psychosis might have male-specific alterations in social cognition in association with the expression of NOTCH1 or JAG1. In our first episode psychosis cohort, we observed a specific correlation between the expression of JAG1 and a face processing measure only in male patients. The expression of JAG1 was not correlated with any other cognitive and symptomatic scales in all subjects. Together, although we acknowledge the pioneering and exploratory nature, the present work that combines both human and animal studies in a reciprocal manner suggests a novel role for the Notch–JAG pathway in a behavioral dimension(s) related to social cognition in psychotic disorders in a male-specific manner. Nature Publishing Group UK 2022-03-10 /pmc/articles/PMC8913639/ /pubmed/35273151 http://dx.doi.org/10.1038/s41398-022-01867-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Jaaro-Peled, Hanna
Landek-Salgado, Melissa A.
Cascella, Nicola G.
Nucifora, Frederick C.
Coughlin, Jennifer M.
Nestadt, Gerald
Sedlak, Thomas W.
Lavoie, Joelle
De Silva, Sarah
Lee, Somin
Tajinda, Katsunori
Hiyama, Hideki
Ishizuka, Koko
Yang, Kun
Sawa, Akira
Sex-specific involvement of the Notch–JAG pathway in social recognition
title Sex-specific involvement of the Notch–JAG pathway in social recognition
title_full Sex-specific involvement of the Notch–JAG pathway in social recognition
title_fullStr Sex-specific involvement of the Notch–JAG pathway in social recognition
title_full_unstemmed Sex-specific involvement of the Notch–JAG pathway in social recognition
title_short Sex-specific involvement of the Notch–JAG pathway in social recognition
title_sort sex-specific involvement of the notch–jag pathway in social recognition
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8913639/
https://www.ncbi.nlm.nih.gov/pubmed/35273151
http://dx.doi.org/10.1038/s41398-022-01867-4
work_keys_str_mv AT jaaropeledhanna sexspecificinvolvementofthenotchjagpathwayinsocialrecognition
AT landeksalgadomelissaa sexspecificinvolvementofthenotchjagpathwayinsocialrecognition
AT cascellanicolag sexspecificinvolvementofthenotchjagpathwayinsocialrecognition
AT nuciforafrederickc sexspecificinvolvementofthenotchjagpathwayinsocialrecognition
AT coughlinjenniferm sexspecificinvolvementofthenotchjagpathwayinsocialrecognition
AT nestadtgerald sexspecificinvolvementofthenotchjagpathwayinsocialrecognition
AT sedlakthomasw sexspecificinvolvementofthenotchjagpathwayinsocialrecognition
AT lavoiejoelle sexspecificinvolvementofthenotchjagpathwayinsocialrecognition
AT desilvasarah sexspecificinvolvementofthenotchjagpathwayinsocialrecognition
AT leesomin sexspecificinvolvementofthenotchjagpathwayinsocialrecognition
AT tajindakatsunori sexspecificinvolvementofthenotchjagpathwayinsocialrecognition
AT hiyamahideki sexspecificinvolvementofthenotchjagpathwayinsocialrecognition
AT ishizukakoko sexspecificinvolvementofthenotchjagpathwayinsocialrecognition
AT yangkun sexspecificinvolvementofthenotchjagpathwayinsocialrecognition
AT sawaakira sexspecificinvolvementofthenotchjagpathwayinsocialrecognition