Thyroid hormones (THs) play a fundamental role in brain function during development and adulthood. THs are essential regulators of neurogenesis, cell maturation and migration as well myelination and synaptogenesis. Neuroglial cells, including astrocytes and microglia are targets of TH and implicated in TH regulation; however, the regulation is not properly understood at the cellular level. In this study, TH regulation was investigated in vitro using human brain cell lines of astrocytes (Svg-P12) and microglia (HMC3). The cells were exposed to TH receptor agonist (triiodothyronine; T3) and inhibitors (amiodarone/1-850), of different concentrations, followed by RNA extraction and quantitative PCR. The gene expression of known TH regulated genes was studied for a better understanding of TH signaling in astrocytes and microglia. All target genes were successfully measured in both cell types. Interestingly, the regulatory effects of TH in astrocytes and microglia exhibited differences. In astrocytes, T3 exposure resulted in an upregulation in gene expression of DDX54 (DEAD-Box Helicase 54) and KLF9 (Krüppel-like factor 9) but did not affect other genes. Also, THR inhibitor exposure resulted in n upregulation in gene expression of DDX54 (DEAD-Box Helicase 54) and KLF9 (Krüppel-like factor 9) but did not affect other genes. Also, THR inhibitor exposure resulted in downregulation in gene expression of KLF9, NES (Nestin), PTGDS (Prostaglandin D2 Synthase) and MAPT (Microtubule Associated Protein Tau). In contrast, none of the TH regulated genes demonstrated a statistical significance in T3-treated microglia compared to control cells. However, THR inhibitor exposure resulted in a downregulation in gene expression of KLF9 and DDX54 and an upregulation of NES, PTGDS and MAPT. The observed differences indicate that TH signaling and regulation is different in microglia and astrocytes. The The differential signaling suggests that T3 does not regulate all of its target genes directly; rather, the regulatory effects of T3 may be exerted through complex mechanisms with other key factors involved. It can be concluded that astrocytes and microglia play important roles as mediators of the effects of THs in CNS development and function. However, further analysis is needed to acknowledge other key factors and TH signaling mechanisms influencing the gene expression in neuroglia.
| Identifer | oai:union.ndltd.org:UPSALLA1/oai:DiVA.org:oru-98136 |
| Date | January 2021 |
| Creators | Levisson, Renée |
| Publisher | Örebro universitet, Institutionen för naturvetenskap och teknik |
| Source Sets | DiVA Archive at Upsalla University |
| Language | English |
| Detected Language | English |
| Type | Student thesis, info:eu-repo/semantics/bachelorThesis, text |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess |
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