Abstract

Calcium (Ca²⁺) signaling is a fundamental process governing a multitude of cellular functions in the central nervous system, including neurotransmission, gene expression, and cell survival. Photodynamic treatment (PDT), a therapeutic approach utilizing photosensitizers and light, is known to induce oxidative stress, but its precise impact on the intricate Ca²⁺ regulatory mechanisms in neural tissue remains poorly understood. This study investigated the immediate and downstream effects of PDT on Ca²⁺ homeostasis and subsequent signaling pathways in primary cultures of both neurons and glial cells. Using fluorescence microscopy and Ca²⁺-sensitive dyes, we quantified changes in resting intracellular Ca²⁺ concentrations and the kinetics of Ca²⁺ transients following PDT exposure. Our key findings demonstrate a significant, dose-dependent disruption of Ca²⁺ homeostasis, characterized by an initial massive influx of Ca²⁺, particularly in neurons, followed by a sustained elevation in both cell types. This dysregulation was linked to compromised plasma membrane integrity and mitochondrial dysfunction, leading to altered Ca²⁺-dependent signaling cascades. The results highlight the vulnerability of neural cells to PDT-induced Ca²⁺ overload and provide critical insights into the cellular mechanisms underlying PDT's effects, which is vital for optimizing therapeutic protocols and mitigating potential neurotoxicity.