TWEAKing the Hippocampus: The Effects of TWEAK on the Genomic Fabric of the Hippocampus in a Neuropsychiatric Lupus Mouse Model

Abstract

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 (Dnajc28, Syne2, transthyretin) 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.

Theory and Applications of the (Cardio) Genomic Fabric Approach to Post-Ischemic and Hypoxia-Induced Heart Failure

“…As one may note in Figure 1 , the hypoxia not only changed the expression levels of the individual genes, but also their expression control and expression coordination in functional pathways. Substantial changes in the genes’ expression control and inter-coordination were constant findings in all previous GFP studies on diseases on samples collected from both humans [ 26 , 30 , 31 , 33 , 55 ] and animal models (e.g., [ 57 , 58 , 59 , 60 ]). We believe that such rich additional information could be instrumental in developing a personalized genomic medicine.…”

“…The independence and complementarity of the three types of characteristics were proven previously for genes within the mTOR signaling pathway and evading apoptosis in human prostate [ 26 , 55 ], apoptosis in human thyroid [ 31 ], and chemokine signaling in human kidney [ 33 ]. They were also proven for chemokine signaling in mouse cortex [ 57 ], PI3K–AKT signaling in mouse hippocampus [ 58 ], and ion channels and transporters in mouse heart myocardia of each of the four chambers [ 6 ]. Regardless of the used high-throughput transcriptomic platform (RNA-sequencing, microarray, Affymetrix etc.…”

“…So far, the GFP power to characterize the organization of the transcriptome was successfully tested in several other studies on neurological diseases (e.g., [ 35 , 57 , 58 , 59 ]), pulmonary hypertension [ 60 ], and cancers [ 26 , 30 , 31 , 33 , 55 , 70 ]. GFP proved also its ability to characterize the transcriptomic networks linking ionic channels and transporters across the heart chambers [ 6 ] as well as different cell types in insert systems [ 75 ].…”

Personalized 3-Gene Panel for Prostate Cancer Target Therapy

“…These genes were used only to illustrate the independence of AVE, REV and COR, but any other gene subset would equally prove the independence. It was also proved in previous publications for apoptosis in human thyroid [21], chemokine signaling in human kidney [18] and mouse cortex [80], evading apoptosis in human prostate [33], ionic channels in mouse heart [81] and PI3K-AKT signaling in mouse hippocampus [82]).…”

Personalized 1-2-3-Gene(s) Tickets to Cancer-Free Prostate

“…The independence and complementarity of these types of characteristics was proved in Figure 1. It was also proved in previous publications for apoptosis in human thyroid [21], chemokine signaling in human kidney [18] and mouse cortex [65], evading apoptosis in human prostate [31], ionic channels in mouse heart [66], and PI3K-AKT signaling in mouse hippocampus [67]).…”