Objective: In this study, we aimed to investigate whether hypoxic conditions can activate cerebral astrocytes and explore their protective effects on α-synuclein pre-formed fibril (PFF)-treated cortical neurons.
Background: Various genetic, environmental, and lifestyle factors contribute to the pathogenesis of Parkinson’s disease (PD), among which smoking is a known protective factor against PD. However, its mechanism has not yet been fully elucidated. Previous studies showed that hypoxia exposure had a beneficial effect on patients with neurological disorders. In experimental research, hypoxia exposure activated protective A2-type astrocytes in mice. Thus, smoking-induced mild hypoxic conditions may positively affect PD pathogenesis, especially via A2-type astrocyte activation.
Method: We investigated the activation levels of primary cortical astrocytes depending on various hypoxic conditions and determined the appropriate conditions for this study. Hypoxia-exposed astrocyte-conditioned medium (hypoxic-ACM) was treated on α-synuclein PFF-treated primary cortical neurons. Cell viability and α-synuclein and p-α-synuclein levels in the neurons were examined. Furthermore, we analyzed DNA expression patterns of hypoxia-exposed astrocytes.
Results: We found that short-term rather than long-term exposure to hypoxic conditions dramatically activated cortical astrocytes. The hypoxic-ACM significantly reduced the death of α-synuclein PFF-treated cortical neurons and toxic p-α-synuclein formation compared to control-ACM. Further, hypoxia-exposed astrocytes demonstrated a different DNA expression profile compared to control astrocytes.
Conclusion: Mild hypoxic condition activated cortical astrocytes, which demonstrated a protective effect on α-synuclein PFF-treated cortical neurons, at least in part, by modifying astrocyte DNA expression. Our findings provide a possible explanation on the protective effects of smoking on PD pathogenesis and suggest that hypoxic conditions can be used clinically as a disease-modifying strategy.
To cite this abstract in AMA style:
M. Kim, S-H. Kim, HN. Choi, JY. Je, SP. Yun. Hypoxia‑induced astrocyte activation and its protective effect on Parkinson’s disease [abstract]. Mov Disord. 2023; 38 (suppl 1). https://www.mdsabstracts.org/abstract/hypoxia%e2%80%91induced-astrocyte-activation-and-its-protective-effect-on-parkinsons-disease/. Accessed May 16, 2025.« Back to 2023 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/hypoxia%e2%80%91induced-astrocyte-activation-and-its-protective-effect-on-parkinsons-disease/