Transcriptome Analysis Reveals Neuroprotective aspects of Human Reactive Astrocytes induced by Interleukin 1β

Abstract

Reactive astrogliosis is a critical process in neuropathological conditions and neurotrauma. Although it has been suggested that it confers neuroprotective effects, the exact genomic mechanism has not been explored. The prevailing dogma of the role of astrogliosis in inhibition of axonal regeneration has been challenged by recent findings in rodent model’s spinal cord injury, demonstrating its neuroprotection and axonal regeneration properties. We examined whether their neuroprotective and axonal regeneration potentials can be identify in human spinal cord reactive astrocytes in vitro. Here, reactive astrogliosis was induced with IL1β. Within 24 hours of IL1β induction, astrocytes acquired reactive characteristics. Transcriptome analysis of over 40000 transcripts of genes and analysis with PFSnet subnetwork revealed upregulation of chemokines and axonal permissive factors including FGF2, BDNF, and NGF. In addition, most genes regulating axonal inhibitory molecules, including ROBO1 and ROBO2 were downregulated. There was no increase in the gene expression of “Chondroitin Sulfate Proteoglycans” (CSPGs’) clusters. This suggests that reactive astrocytes may not be the main CSPG contributory factor in glial scar. PFSnet analysis also indicated an upregulation of “Axonal Guidance Signaling” pathway. Our result suggests that human spinal cord reactive astrocytes is potentially neuroprotective at an early onset of reactive astrogliosis.

Exosomal MicroRNAs Released by Activated Astrocytes as Potential Neuroinflammatory Biomarkers

“…IL-1β was chosen because it is a primary cytokine released by activated microglia at the site of brain injury and is a prominent contributor to inflammatory signaling cascades. Previous studies have shown that cellular and/or exosomal miRNAs of mouse astrocytes are dysregulated in response to inflammatory stress [13,16]. However, there are no reports on the release of astrocytic exosomal miRNAs from activated human astrocytes.…”

“…Few studies have reported miRNA transcriptome analysis of astrocytes from adult and human fetal brains. These studies have identified a subset of astrocyte-specific miRNAs under the normal physiological resting stage as well as IL-1β induced neuroinflammatory stress [12,13]. In this study, our goal was to identify exosomal miRNAs secreted by human astrocytes under proinflammatory and oxidative stress conditions and compare them to exosomal miRNAs released from resting astrocytes.…”

Intraventricular CXCL12 is neuroprotective and increases neurogenesis in a murine model of stroke

“…Astrocytes are commonly thought to be involved in negative responses through glial scar formation and inhibition of axonal regeneration (Silver et al 2014). But new data describe that astrocytes appear to possess a high potential for regeneration and neuroprotection following stroke (Sofroniew and Vinters 2010;Becerra-Calixto and Cardona-Gómez 2017;Teh et al 2017). Astrocytes are involved in a large number of key processes essentials to keep integrity of the nervous system, such as regulating the vascular tone, removing excess glutamate in synaptic cleft and preventing excitotoxicity, releasing neurotrophic factors and antioxidants and promoting synaptogenesis (López-Valdés et al 2014).…”

IncreasedAPOEε4expression is associated with reactive A1 astrocytes and the difference in Alzheimer Disease risk from diverse ancestral backgrounds

“…To further characterize cluster 21, we compared the transcriptome of this cluster with the other astrocyte clusters (4, 8 and 16). Analysis of the identified DEG from this analysis indicates that cluster 21 preferentially expressed markers of reactive astrocytes 18,19 , with significantly higher levels of GFAP, VIM, LGALS1, FGF2, and HSBP1 compared to other astrocyte clusters ( Supplementary Table 7). Interestingly, compared to the other astrocyte clusters, Cluster 21 also overexpressed IFITM3, CHI3L1, and B2M, which are specifically upregulated by neuroinflammation in A1-type reactive astrocytes in mice 18 .…”

“…http://adsn.ddnetbio.com). Identification of the reactive A1 astrocyte cluster used available literature characterizing transcriptome of that cell type18,19,41 …”