When neurons encounter nanoobjects: spotlight on calcium signalling

Nanosized objects are increasingly present in everyday life and in specialized technological applications. In recent years, as a consequence of concern about their potential adverse effects, intense research effort has led to a better understanding of the physicochemical properties that underlie their biocompatibility or potential toxicity, setting the basis for a rational approach to their use in the different fields of application. Among the functional parameters that can be perturbed by interaction between nanoparticles (NPs) and living structures, calcium homeostasis is one of the key players and has been actively investigated. One of the most relevant biological targets is represented by the nervous system (NS), since it has been shown that these objects can access the NS through several pathways; moreover, engineered nanoparticles are increasingly developed to be used for imaging and drug delivery in the NS. In neurons, calcium homeostasis is tightly regulated through a complex set of mechanisms controlling both calcium increases and recovery to the basal levels, and even minor perturbations can have severe consequences on neuronal viability and function, such as excitability and synaptic transmission. In this review, we will focus on the available knowledge about the effects of NPs on the mechanisms controlling calcium signalling and homeostasis in neurons. We have taken into account the data related to environmental NPs, and, in more detail, studies employing engineered NPs, since their more strictly controlled chemical and physical properties allow a better understanding of the relevant parameters that determine the biological responses they elicit. The literature on this specific subject is all quite recent, and we have based the review on the data present in papers dealing strictly with nanoparticles and calcium signals in neuronal cells; while they presently amount to about 20 papers, and no related review is available, the field is rapidly growing and some relevant information is already available. A few general findings can be summarized: most NPs interfere with neuronal calcium homeostasis by interactions at the plasmamembrane, and not following their internalization; influx from the extracellular medium is the main mechanism involved; the effects are dependent in a complex way from concentration, size and surface properties.