TWEAKing the Hippocampus: The Effects of TWEAK on the Genomic Fabric of the Hippocampus in a Neuropsychiatric Lupus Mouse Model
Neuropsychiatric manifestations of systemic lupus erythematosus (SLE), specifically cognitive dysfunction and mood disorders, are widely prevalent in SLE patients, and yet poorly understood. TNF-like weak inducer of apoptosis (TWEAK) has previously been implicated in the pathogenesis of neuropsychia...
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MDPI AG
2021-07-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/12/8/1172 |
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| author | Dumitru A. Iacobas Jing Wen Sanda Iacobas Chaim Putterman Noa Schwartz |
| author_facet | Dumitru A. Iacobas Jing Wen Sanda Iacobas Chaim Putterman Noa Schwartz |
| author_sort | Dumitru A. Iacobas |
| collection | DOAJ |
| description | Neuropsychiatric manifestations of systemic lupus erythematosus (SLE), specifically cognitive dysfunction and mood disorders, are widely prevalent in SLE patients, and yet poorly understood. TNF-like weak inducer of apoptosis (TWEAK) has previously been implicated in the pathogenesis of neuropsychiatric lupus (NPSLE), and we have recently shown its effects on the transcriptome of the cortex of the lupus-prone mice model MRL/lpr. As the hippocampus is thought to be an important focus of NPSLE processes, we explored the TWEAK-induced transcriptional changes that occur in the hippocampus, and isolated several genes (<i>Dnajc28</i>, <i>Syne2</i>, <i>transthyretin</i>) and pathways (PI3K-AKT, as well as chemokine-signaling and neurotransmission pathways) that are most differentially affected by TWEAK activation. While the functional roles of these genes and pathways within NPSLE need to be further investigated, an interesting link between neuroinflammation and neurodegeneration appears to emerge, which may prove to be a promising novel direction in NPSLE research. |
| first_indexed | 2024-03-10T08:47:58Z |
| format | Article |
| id | doaj.art-9fdd8ca524014dc9ba6a24912fc85325 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T08:47:58Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-9fdd8ca524014dc9ba6a24912fc853252023-11-22T07:45:33ZengMDPI AGGenes2073-44252021-07-01128117210.3390/genes12081172TWEAKing the Hippocampus: The Effects of TWEAK on the Genomic Fabric of the Hippocampus in a Neuropsychiatric Lupus Mouse ModelDumitru A. Iacobas0Jing Wen1Sanda Iacobas2Chaim Putterman3Noa Schwartz4Personalized Genomics Laboratory, Center for Computational Systems Biology, Roy G Perry College of Engineering, Prairie View A&M University, Prairie View, TX 77446, USADepartment of Medicine (Rheumatology), Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Pathology, New York Medical College, Valhalla, NY 10595, USADepartment of Medicine (Rheumatology), Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Medicine (Rheumatology), Albert Einstein College of Medicine, Bronx, NY 10461, USANeuropsychiatric manifestations of systemic lupus erythematosus (SLE), specifically cognitive dysfunction and mood disorders, are widely prevalent in SLE patients, and yet poorly understood. TNF-like weak inducer of apoptosis (TWEAK) has previously been implicated in the pathogenesis of neuropsychiatric lupus (NPSLE), and we have recently shown its effects on the transcriptome of the cortex of the lupus-prone mice model MRL/lpr. As the hippocampus is thought to be an important focus of NPSLE processes, we explored the TWEAK-induced transcriptional changes that occur in the hippocampus, and isolated several genes (<i>Dnajc28</i>, <i>Syne2</i>, <i>transthyretin</i>) and pathways (PI3K-AKT, as well as chemokine-signaling and neurotransmission pathways) that are most differentially affected by TWEAK activation. While the functional roles of these genes and pathways within NPSLE need to be further investigated, an interesting link between neuroinflammation and neurodegeneration appears to emerge, which may prove to be a promising novel direction in NPSLE research.https://www.mdpi.com/2073-4425/12/8/1172neuropsychiatric lupushippocampusTNF-like weak inducer of apoptosis (TWEAK)Tnfsf12Fn14Tnfrsf12a |
| spellingShingle | Dumitru A. Iacobas Jing Wen Sanda Iacobas Chaim Putterman Noa Schwartz TWEAKing the Hippocampus: The Effects of TWEAK on the Genomic Fabric of the Hippocampus in a Neuropsychiatric Lupus Mouse Model Genes neuropsychiatric lupus hippocampus TNF-like weak inducer of apoptosis (TWEAK) Tnfsf12 Fn14 Tnfrsf12a |
| title | TWEAKing the Hippocampus: The Effects of TWEAK on the Genomic Fabric of the Hippocampus in a Neuropsychiatric Lupus Mouse Model |
| title_full | TWEAKing the Hippocampus: The Effects of TWEAK on the Genomic Fabric of the Hippocampus in a Neuropsychiatric Lupus Mouse Model |
| title_fullStr | TWEAKing the Hippocampus: The Effects of TWEAK on the Genomic Fabric of the Hippocampus in a Neuropsychiatric Lupus Mouse Model |
| title_full_unstemmed | TWEAKing the Hippocampus: The Effects of TWEAK on the Genomic Fabric of the Hippocampus in a Neuropsychiatric Lupus Mouse Model |
| title_short | TWEAKing the Hippocampus: The Effects of TWEAK on the Genomic Fabric of the Hippocampus in a Neuropsychiatric Lupus Mouse Model |
| title_sort | tweaking the hippocampus the effects of tweak on the genomic fabric of the hippocampus in a neuropsychiatric lupus mouse model |
| topic | neuropsychiatric lupus hippocampus TNF-like weak inducer of apoptosis (TWEAK) Tnfsf12 Fn14 Tnfrsf12a |
| url | https://www.mdpi.com/2073-4425/12/8/1172 |
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