Light vs. Brain Cells: How Photodynamic Therapy Impacts Neurons & Astrocytes
"Uncover the surprising effects of photodynamic therapy (PDT) on brain cells and learn how this cancer treatment can trigger calcium signals and lipid peroxidation in neurons and astrocytes."
Photodynamic therapy (PDT) is a powerful method for destroying brain tumors by producing reactive oxygen species (ROS), leading to oxidative stress and the death of cancerous cells. Radachlorin, a chlorine derivative photosensitizer, is often used in PDT due to its ability to quickly accumulate in tumor tissue and rapidly clear from the body. However, the effects of radachlorin on healthy brain cells remain unclear.
One major effect of PDT is the induction of reactive oxygen species (ROS). While excessive ROS production can trigger cell death, smaller amounts can play a physiological role, including acting as stimuli for calcium signaling. Calcium ions are vital for regulating intracellular processes and cell-to-cell communication, especially in excitable cells like neurons and astrocytes.
Research has shown that PDT can increase intracellular calcium levels by activating calcium channels or releasing calcium from internal stores. Given the importance of understanding how PDT impacts healthy brain cells, this article delves into the specific effects of radachlorin on calcium signaling and lipid peroxidation in neurons and astrocytes.
Calcium Signals and Brain Cell Response: What Happens?
Researchers investigated how radachlorin affects primary cultures of cortical neurons and astrocytes using live cell imaging. They found that irradiation in the presence of radachlorin induced calcium signals in both neurons and astrocytes, indicating a direct impact on these brain cells.
- Internal Calcium Stores: The calcium signal depended on internal calcium stores within the cells. Even in a calcium-free environment, the signal persisted.
- Endoplasmic Reticulum (ER): Blocking the ER's calcium stores with thapsigargin (an inhibitor of SERCA) eliminated the calcium response.
- Phospholipase C (PLC): Inhibitors of phospholipase C (U73122 and Trolox) suppressed the calcium response, indicating PLC's involvement.
- Lipid Peroxidation: Radachlorin induced lipid peroxidation in both neurons and astrocytes.
Protecting the Brain: Implications of PDT on Healthy Tissue
The study highlights that irradiation with radachlorin induces lipid peroxidation in neurons and astrocytes, either directly or indirectly through ROS production. The fact that Trolox, an antioxidant, blocked the effect of radachlorin irradiation further supports the role of ROS.
The photodynamic effect of radachlorin may induce ROS production that triggers lipid peroxidation. Oxidized lipids then stimulate phospholipase C, leading to IP3 production and calcium release from the ER.
While PDT is valuable for cancer treatment, this research underscores the importance of considering its effects on healthy brain tissue. Photo-induced calcium signals in neurons and astrocytes could be protective, stimulating processes for cell protection or utilizing oxidized lipids. However, in certain brain areas, this signal might interfere with normal regulatory processes within the central nervous system. Since calcium signaling is energy-intensive, prolonged elevations in calcium, combined with disrupted energy metabolism from PDT, could potentially damage healthy tissue.