Uncovering the role of neuregulin-1 in regulating microglia properties: in vitro studies
| dc.contributor.author | Mohammadzadeh Shahriary, Ghazaleh | |
| dc.contributor.examiningcommittee | Dhingra, Sanjiv (Physiology and Pathophysiology) Eftekharpour, Eftekhar (Physiology and Pathophysiology) Kauppinen, Tiina (Pharmacology and Therapeutics) | en_US |
| dc.contributor.supervisor | Karimi-Abdolrezaee, Soheila (Physiology and Pathophysiology) | en_US |
| dc.date.accessioned | 2018-08-15T15:31:14Z | |
| dc.date.available | 2018-08-15T15:31:14Z | |
| dc.date.issued | 2018-08-04 | en_US |
| dc.date.submitted | 2018-08-05T02:39:04Z | en |
| dc.degree.discipline | Physiology and Pathophysiology | en_US |
| dc.degree.level | Master of Science (M.Sc.) | en_US |
| dc.description.abstract | Microglia are resident immune cells of the central nervous system, which in concert with astrocytes and peripherally recruited immune cells initiate a pro-inflammatory response after injury and disease that results in oligodendroglial death and myelin damage. We have shown that down-regulation of a neuronally-derived growth factor, neuregulin-1, in demyelinating lesions of the spinal cord is an underlying mechanism for insufficient spontaneous oligodendrogenesis and remyelination. Recent evidence suggests that Nrg-1 treatment positively regulates the repair process and remyelination by modulating neuroinflammation. The goal of the present study was to determine the role of Nrg-1 in regulating microglia response in normal and injury state. In primary in vitro systems, we demonstrate a positive role for Nrg-1 in regulating microglia activity and the impact of Nrg-1 treatment on the effects of microglia on the behavior of neural precursor cells (NPCs). Using an array of cellular and molecular assays, we found that Nrg-1 attenuated the transcript expression of several pro-inflammatory markers such as tumor necrosis factor- (TNF-) α, interleukin- (IL-) 6, CD86 and the production of nitric oxide (NO). In addition, Nrg-1 restored the suppressed phagocytic ability in M1-polarized microglia cultures. Our findings showed that microglia conditioned media (MCM) from Nrg-1 treated M1-polarized microglia cultures promoted migration and proliferation of NPCs. Hence, our findings suggest that Nrg-1 therapy could be exploited to foster a pro-regenerative phenotype in microglia, which is supportive of repair and regeneration following CNS injuries and diseases. | en_US |
| dc.description.note | October 2018 | en_US |
| dc.identifier.uri | http://hdl.handle.net/1993/33201 | |
| dc.language.iso | eng | en_US |
| dc.rights | open access | en_US |
| dc.subject | Neuregulin-1 | en_US |
| dc.subject | Microglia | en_US |
| dc.subject | In vitro studies | en_US |
| dc.subject | NPCs | en_US |
| dc.title | Uncovering the role of neuregulin-1 in regulating microglia properties: in vitro studies | en_US |
| dc.type | master thesis | en_US |