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Transcriptome Profiling Reveals Novel Candidate Genes Related to Hippocampal Dysfunction in SREBP-1c Knockout Mice

Lipid homeostasis is an important component of brain function, and its disturbance causes several neurological disorders, such as Huntington’s, Alzheimer’s, and Parkinson’s diseases as well as mood disorders. Sterol regulatory element-binding protein-1c (SREBP-1c) is a key modulatory molecule involv...

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Autores principales: Ang, Mary Jasmin, Kim, Juhwan, Lee, Sueun, Kim, Sung-Ho, Kim, Jong-Choon, Jeon, Tae-Il, Im, Seung-Soon, Moon, Changjong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313053/
https://www.ncbi.nlm.nih.gov/pubmed/32531902
http://dx.doi.org/10.3390/ijms21114131
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author Ang, Mary Jasmin
Kim, Juhwan
Lee, Sueun
Kim, Sung-Ho
Kim, Jong-Choon
Jeon, Tae-Il
Im, Seung-Soon
Moon, Changjong
author_facet Ang, Mary Jasmin
Kim, Juhwan
Lee, Sueun
Kim, Sung-Ho
Kim, Jong-Choon
Jeon, Tae-Il
Im, Seung-Soon
Moon, Changjong
author_sort Ang, Mary Jasmin
collection PubMed
description Lipid homeostasis is an important component of brain function, and its disturbance causes several neurological disorders, such as Huntington’s, Alzheimer’s, and Parkinson’s diseases as well as mood disorders. Sterol regulatory element-binding protein-1c (SREBP-1c) is a key modulatory molecule involved in lipid homeostasis in the central nervous system. However, little is known about the biological effects of SREBP-1c in the brain. Our previous study uncovered that mice deficient in SREBP-1c exhibit schizophrenia-like behaviors. To investigate whether there are novel molecular mechanisms involved in the neurological aberrations caused by SREBP-1c deficiency, we analyzed the transcriptomes of the hippocampus of SREBP-1c knockout (KO) mice and wild-type mice. We found seven differentially expressed genes (three up-regulated and four down-regulated genes) in the hippocampus of SREBP-1c KO mice. For further verification, we selected the three most significantly changed genes: glucagon-like peptide 2 receptors (GLP2R) involved in hippocampal neurogenesis and neuroplasticity as well as in cognitive impairments; necdin (NDN) which is related to neuronal death and neurodevelopmental disorders; and Erb-B2 receptor tyrosine kinase 4 (ERBB4) which is a receptor for schizophrenia-linked protein, neuregulin-1. The protein levels of GLP2R and NDN were considerably decreased, but the level of ERBB4 was significantly increased in the hippocampus of SREBP-1c KO mice. However, further confirmation is warranted to establish the translatability of these findings from this rodent model into human patients. We suggest that these data provide novel molecular evidence for the modulatory role of SREBP-1c in the mouse hippocampus.
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spelling pubmed-73130532020-06-29 Transcriptome Profiling Reveals Novel Candidate Genes Related to Hippocampal Dysfunction in SREBP-1c Knockout Mice Ang, Mary Jasmin Kim, Juhwan Lee, Sueun Kim, Sung-Ho Kim, Jong-Choon Jeon, Tae-Il Im, Seung-Soon Moon, Changjong Int J Mol Sci Article Lipid homeostasis is an important component of brain function, and its disturbance causes several neurological disorders, such as Huntington’s, Alzheimer’s, and Parkinson’s diseases as well as mood disorders. Sterol regulatory element-binding protein-1c (SREBP-1c) is a key modulatory molecule involved in lipid homeostasis in the central nervous system. However, little is known about the biological effects of SREBP-1c in the brain. Our previous study uncovered that mice deficient in SREBP-1c exhibit schizophrenia-like behaviors. To investigate whether there are novel molecular mechanisms involved in the neurological aberrations caused by SREBP-1c deficiency, we analyzed the transcriptomes of the hippocampus of SREBP-1c knockout (KO) mice and wild-type mice. We found seven differentially expressed genes (three up-regulated and four down-regulated genes) in the hippocampus of SREBP-1c KO mice. For further verification, we selected the three most significantly changed genes: glucagon-like peptide 2 receptors (GLP2R) involved in hippocampal neurogenesis and neuroplasticity as well as in cognitive impairments; necdin (NDN) which is related to neuronal death and neurodevelopmental disorders; and Erb-B2 receptor tyrosine kinase 4 (ERBB4) which is a receptor for schizophrenia-linked protein, neuregulin-1. The protein levels of GLP2R and NDN were considerably decreased, but the level of ERBB4 was significantly increased in the hippocampus of SREBP-1c KO mice. However, further confirmation is warranted to establish the translatability of these findings from this rodent model into human patients. We suggest that these data provide novel molecular evidence for the modulatory role of SREBP-1c in the mouse hippocampus. MDPI 2020-06-10 /pmc/articles/PMC7313053/ /pubmed/32531902 http://dx.doi.org/10.3390/ijms21114131 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ang, Mary Jasmin
Kim, Juhwan
Lee, Sueun
Kim, Sung-Ho
Kim, Jong-Choon
Jeon, Tae-Il
Im, Seung-Soon
Moon, Changjong
Transcriptome Profiling Reveals Novel Candidate Genes Related to Hippocampal Dysfunction in SREBP-1c Knockout Mice
title Transcriptome Profiling Reveals Novel Candidate Genes Related to Hippocampal Dysfunction in SREBP-1c Knockout Mice
title_full Transcriptome Profiling Reveals Novel Candidate Genes Related to Hippocampal Dysfunction in SREBP-1c Knockout Mice
title_fullStr Transcriptome Profiling Reveals Novel Candidate Genes Related to Hippocampal Dysfunction in SREBP-1c Knockout Mice
title_full_unstemmed Transcriptome Profiling Reveals Novel Candidate Genes Related to Hippocampal Dysfunction in SREBP-1c Knockout Mice
title_short Transcriptome Profiling Reveals Novel Candidate Genes Related to Hippocampal Dysfunction in SREBP-1c Knockout Mice
title_sort transcriptome profiling reveals novel candidate genes related to hippocampal dysfunction in srebp-1c knockout mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313053/
https://www.ncbi.nlm.nih.gov/pubmed/32531902
http://dx.doi.org/10.3390/ijms21114131
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