Work

The role of REST in regulating the BDNF/TrkB signalling pathway in nano-alumina induced cognitive dysfunction in zebrafish

Year: 2025

Type: article

Abstract: Synaptic plasticity is fundamental for cognitive development and brain function. Aluminium nanoparticles (AlNPs), widely used in industrial and consumer products, pose potential neurotoxic risks, particularly during early neurodevelopment. However, their effects on synaptic plasticity and cognitive outcomes remain poorly understood. Therefore, in this study, we established a zebrafish embryonic AlNP exposure model to assess the long-term impacts of AlNP exposure on neurodevelopment and cognition. Additionally, we used morpholino-mediated gene knockdown to investigate the role of repressor element 1-silencing transcription factor (REST) in AlNP-induced neurotoxicity. Behavioural assays at 7 days post-fertilization, 1 month, and adulthood revealed that AlNP exposure or brain-derived neurotrophic factor (BDNF) knockdown impaired locomotion, escape responses, and learning/memory, whereas REST knockdown mitigated the AINP-induced behavioural impairments. Electrophysiological recordings showed that AlNP exposure and BDNF knockdown reduced neuronal firing activity and synchrony, while REST knockdown enhanced these responses. Morphological analysis demonstrated reduced dendritic spine density after AlNP exposure or BDNF knockdown, but increased density after REST knockdown. Molecular assays showed that AlNP exposure and BDNF knockdown upregulated REST and downregulated BDNF/TrkB signalling and synaptic plasticity-related proteins, whereas REST knockdown exerted opposite effects; REST knockdown + AlNP exposure partially restored signalling activity and synaptic protein expression. These findings indicate that AlNPs impair synaptic plasticity and cognitive function by disrupting REST-regulated BDNF/TrkB signalling, providing new mechanistic insights into the neurotoxic effects of environmental nanomaterial exposure.

Source: Ecotoxicology and Environmental Safety

DOI: 10.1016/j.ecoenv.2025.118998