Cytotoxicity and Effects on the Synapsis Induced by Pure Cylindrospermopsin in an E17 Embryonic Murine Primary Neuronal Culture in a Concentration- and Time-Dependent Manner

Abstract

Cylindrospermopsin (CYN) is a cyanotoxin whose incidence has been increasing in the last decades. Due to its capacity to exert damage at different levels of the organism, it is considered a cytotoxin. Although the main target organ is the liver, recent studies indicate that CYN has potential toxic effects on the nervous system, both in vitro and in vivo. Thus, the aim of the present work was to study the effects of this cyanotoxin on neuronal viability and synaptic integrity in murine primary cultures of neurons exposed to environmentally relevant concentrations (0–1 µg/mL CYN) for 12, 24, and 48 h. The results demonstrate a concentration- and time-dependent decrease in cell viability; no cytotoxicity was detected after exposure to the cyanotoxin for 12 h, while all of the concentrations assayed decreased this parameter after 48 h. Furthermore, CYN was also demonstrated to exert damage at the synaptic level in a murine primary neuronal culture in a concentration- and time-dependent manner. These data highlight the importance of studying the neurotoxic properties of this cyanotoxin in different experimental models.

Cytotoxic Effects and Oxidative Stress Produced by a Cyanobacterial Cylindrospermopsin Producer Extract versus a Cylindrospermopsin Non-Producing Extract on the Neuroblastoma SH-SY5Y Cell Line

“…Concerning the effects of pure CYN in cytotoxicity in neuronal cell models, Takser et al [49] also obtained a concentration-dependent effect after exposure to 0.042 and 4.2 µg/mL in N2a murine neuroblastoma derived cells and BV-2 microglia murine cells with N2a cells being more sensitive to CYN than BV-2 cells, which highlights the importance of the experimental model. Furthermore, the effects of pure CYN have been investigated in terms of synapsis effects on murine primary neurons [36], and pure CYN led to a decrease on cell viability at the same concentrations than those tested in the present study, together with a decrease on the number of synapsis at similar concentrations than EC 50 and EC 50/2 in our study [36].…”

“…One of the main targets for this alkaloid is the liver [23], although it has demonstrated to exert toxicity also in the lungs, heart, kidneys, marrow bone, thymus, gastrointestinal tract, adrenal glands, and the immune and nervous systems in several species [4] with this being the reason for its classification as a cytotoxin. However, the studies concerning its effects in the nervous system are still scarce, which is relevant due to the high incidence of degenerative diseases of the nervous system worldwide, and the possible causal contributions from environmental factors [32][33][34][35][36]. In this matter, some studies have been carried out using extracts of CYN-producing cyanobacteria, mainly in vivo [37][38][39][40], but the comparison between the toxic effects produced by a CYNproducing extract versus a CYN-non-producing extract in neuronal models has not been studied yet.…”

Recent Advances in Aptasensing Strategies for Monitoring Phycotoxins: Promising for Food Safety

“…Anatoxins (ATXs) are alkaloid toxins that are highly polar and fully soluble in water. This compound is the most fully natural neurotoxin produced by freshwater cyanobacteria with an LD 50 = 20 µg kg −1 [79]. This toxin is a potent agonist acetylcholinesterase which binds to nicotinic acetylcholine receptors and induces conformational changes in the postsynaptic receptor ion channel complex.…”