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Comparative neurotoxicity of Bisphenol-A and aluminum chloride in adult zebrafish: Behavioral disruption and region-specific neuropathology under chronic exposure

Year: 2025

Type: article

Abstract: The escalating environmental presence of neuroactive pollutants such as Bisphenol-A (BPA) and aluminum chloride (AlCl₃) raises critical concerns regarding their long-term effects on cognitive health. This study presents a comparative neurotoxicity model using adult zebrafish ( Danio rerio ) exposed to a 21-day static immersion protocol with environmentally relevant doses (2 and 4 mg/L). Neurobehavioral changes were assessed using the novel tank diving test (NTDT) and a color-based T-maze, combined with detailed histopathological scoring. BPA induced markedly stronger neurobehavioral and neuropathological effects than AlCl₃. BPA exposure caused dose-dependent reductions in swim velocity and distance travelled, heightened anxiety-like behavior, and cognitive inflexibility with reduced exploratory transitions and spatial learning. Histology revealed extensive vacuolation, neuronal pyknosis, and perineural congestion in the telencephalic and diencephalic regions, confirming widespread neurodegeneration. In contrast, AlCl₃ produced moderate impairments, with neuropathology primarily confined to the cerebellum and thalamus. These differential effects suggest distinct mechanisms: BPA may disrupt synaptic plasticity and hypothalamic–pituitary–interrenal (HPI) axis signaling, whereas AlCl₃ likely involves mitochondrial dysfunction and tauopathy. By integrating behavioral phenotyping with region-specific neuropathology, this model highlights the translational relevance of adult zebrafish for regulatory toxicology and human health risk assessment of aquatic neurotoxicants. • Comparative, side-by-side evaluation of Bisphenol-A (BPA) and Aluminum chloride (AlCl₃) neurotoxicity using adult zebrafish. • BPA exposure induced pronounced anxiety-like behavior, cognitive impairment, and hypoactivity in a dose-dependent manner. • AlCl₃ exposure caused moderate behavioral alterations with region-specific neurodegeneration in the cerebellum and thalamus. • Histopathological analysis confirmed widespread neuronal damage in BPA groups, especially in the telencephalon and diencephalon. • The study presents an optimized chronic zebrafish model for evaluating environmental neurotoxicants under realistic exposure conditions.

Source: Toxicology Reports

DOI: 10.1016/j.toxrep.2025.102161