The Neurotoxic Effect of Environmental Temperature Variation in Adult Zebrafish (Danio rerio)

Neurotoxicity consists of the altered functionality of the nervous system caused by ex- posure to chemical agents or altered chemical–physical parameters. The neurotoxic effect can be evaluated from the molecular to the behavioural level. The zebrafish Danio rerio is a model organism used in many research fields, including ecotoxicology and neurotoxicology. Recent studies by our research group have demonstrated that the exposure of adult zebrafish to low (18 ◦C) or high (34 ◦C) temperatures alters their brain proteome and fish behaviour compared to control (26 ◦C). These results showed that thermal variation alters the functionality of the nervous system, suggesting a temperature-induced neurotoxic effect. To demonstrate that temperature variation can be counted among the factors that generate neurotoxicity, eight different protein datasets, previously published by our research group, were subjected to new analyses using an integrated proteomic approach by means of the Ingenuity Pathway Analysis (IPA) software (Release December 2022). The datasets con- sist of brain proteome analyses of wild type adult zebrafish kept at three different temperatures (18 ◦C, 26 ◦C, and 34 ◦C) for 4 days (acute) or 21 days (chronic treatment), and of BDNF+/− and BDNF−/− zebrafish kept at 26 ◦C or 34 ◦C for 21 days. The results (a) demonstrate that thermal alterations generate an effect that can be defined as neurotoxic (p value ≤ 0.05, activation Z score ≤ −2 or ≥2), (b) identify 16 proteins that can be used as hallmarks of the neurotoxic processes common to all the treatments applied and (c) provide three protein panels (p value ≤ 0.05) related to 18 ◦C, 34 ◦C, and BDNF depletion that can be linked to anxiety-like or boldness behaviour upon these treatments.