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Deciphering the role of the 18 kDa Translocator Protein (TSPO) in neuroinflammation

Number of pages48
Master program titleMaîtrise universitaire interdisciplinaire en neurosciences
Defense date2023-06-29
Abstract

The 18 kDa translocator protein (TSPO) is primarily found in the outer mitochondrial membrane and plays different roles in cellular functions. Neuroimaging studies have shown increases in TSPO levels during neuroinflammation, implying its participation in this process. As chronic neuroinflammation has been widely proven to be related to neuropathologies and psychiatric disorders development, TSPO is believed to be a potential target for new diagnostic and therapeutic strategies regarding these pathologies. Though many studies have been performed on this protein, many unknown factors about TSPO’s mechanisms and functions in neuroinflammation remain to be understood. In this research project, we focused on studying some of these characteristics of TSPO using the C6 astrocytic cell line and two mice models that allowed us to better understand the impacts of TSPO in different neuroinflammatory processes. Our in vitro results showed that TSPO overexpression in response to the lipopolysaccharide (LPS)-induced inflammatory model is related to an increase in Tspo gene transcription involving the participation of the STAT3 transcription factor, but also related to an increase in the number of mitochondria per cell. Moreover, TSPO overexpression showed not to affect astrocytic phagocytosis capacity or ATP production. However, we found that LPS induced a reduction of glucose uptake in astrocytes via TSPO-dependent mechanisms, suggesting a partial role of the protein in glucose metabolism. We also showed, using in vivo and ex vivo experiments, that TSPO might not be involved in baseline neuroinflammation-related gene expression, as knockout (KO) of the protein did not impact related mRNA levels, and that astrocytic TSPO deficiency might be compensated by microglial TSPO overexpression in response to the pro-inflammatory cytokine CNTF. These data suggest that TSPO, and specifically astrocytic TSPO, contributes to different cellular functions such as glucose metabolism and pro-inflammatory processes. Despite these results, more studies are needed to better elucidate the exact impacts of this protein on cellular functions and on neuropathology-related neuroinflammation.

eng
Keywords
  • TSPO
  • Neuroinflammation
Citation (ISO format)
NICOLAIDES ALDER, Alekos. Deciphering the role of the <i>18 kDa Translocator Protein</i> (TSPO) in neuroinflammation. 2023.
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Master thesis
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Identifiers
  • PID : unige:170713
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Creation07/10/2023 4:57:02 PM
First validation08/17/2023 10:32:51 AM
Update time08/17/2023 10:32:51 AM
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