Mitochondrial dysfunction mediates neuronal cell response to DMMB photodynamic therapy

Area of Science:

• Cell Biology
• Neuroscience
• Photochemistry

Background:

• Photodynamic therapy (PDT) offers a minimally invasive treatment option for various conditions, including central nervous system (CNS) disorders.
• Neuronal cells exhibit sensitivity to certain photosensitizers (PSs), raising concerns about PDT's safety in the CNS.
• 1,9-dimethyl-methylene blue (DMMB) is a promising PS due to its stability and high singlet-oxygen generation.

Purpose of the Study:

• To investigate the photodamage mechanisms of 1,9-dimethyl-methylene blue (DMMB) in the HT22 hippocampal cell line.
• To elucidate the cellular pathways affected by DMMB-mediated photodynamic therapy (PDT) in neuronal cells.

Main Methods:

• Exposure of HT22 cells to DMMB followed by specific wavelength irradiation.
• Assessment of cell viability, cell death, reactive oxygen species (ROS) production, and mitochondrial membrane potential.
• Analysis of autolysosome presence and expression levels of autophagy-related genes (ATG1, ATG8 homologue GaBarap1, DRAM1).

Main Results:

• DMMB-PDT significantly decreased HT22 cell viability, correlating with increased cell death and overall ROS production.
• Mitochondrial function was impaired, evidenced by increased mitochondrial ROS and decreased mitochondrial membrane potential.
• Autophagic pathways were activated, indicated by increased acidic autolysosomes and altered expression of autophagy-related genes.

Conclusions:

• Mitochondrial dysfunction is a key mechanism underlying DMMB-PDT-induced cytotoxicity in neuronal cells.
• Autophagic dysfunction also contributes significantly to the observed cell death following DMMB-PDT.
• Understanding these mechanisms is crucial for optimizing DMMB-PDT for CNS applications.