Lead-induced neurodegenerative events and abnormal behaviors occur via ORXRergic/GABAARergic mechanisms in a marine teleost

The hindering effects of metals and in particular lead (Pb) are representing a growing threat to aquatic organisms such as fish. This observation derives from toxic concentrations of Pb accounting for altered neurophysiological activities of some interesting teleost models like Thalassoma pavo, a fish species highly known for its host-cleaning symbiosis. In this study, the nominal PbNO3 concentration of 1.6 mg/L was capable of reducing feeding and resting bouts as early as 24 h of exposure while hyperactive swimming episodes were also detected. Such abnormal behaviors were tightly correlated to up-regulated orexin receptor (ORXR) mRNA expression levels in some brain areas such as the lateral thalamic nucleus (+213%) and the optic tectum (+90%) with respect to controls. Interestingly, these transcriptional effects seemed to be attenuated when Pb-exposed fish received either 100 ng/g of ORX-A (−70%) or 0.1 μg/g of γ-aminobutyric acidA receptor (GABAAR) agonist muscimol (MUS; −97%) compared to fish exposed to Pb alone. Moreover, a net neurodegenerative process of the different brain areas was reported after Pb exposure as displayed by their marked amino cupric silver stained cells while these cells were devoid of any staining reaction after treatment with MUS only. Conversely, addition of the GABAAR antagonist bicuculline (BIC; 1 μg/g) moderately (p < 0.05) enhanced Pb-dependent behavioral and neurodegenerative actions. Overall, these first indications strongly point to altered ORXR/GABAAR interactions during neurotoxic events of a metal that by evoking harmful neurobiological dysfunctions may endanger the survival of commercially valuable fish with eventual repercussions on human health.

► Lead reduced feeding and resting bouts along with inducing hyperactive episodes.
► A marked neurodegeneration was reported after lead exposure.
► Lead-dependent ORXR mRNA up-regulations were reduced by ORX-A or MUS.
► Argyrophilic signals were rescued only after MUS treatment.
► BIC enhanced lead-dependent neurobehavioral actions.