Margarida Pereira, Sofia Alves-Pimenta, Carlos Venâncio, Maria de Lurdes Pinto, Bruno Colaço
Olfactory dysfunction is increasingly recognized as an important consequence of exposure to environmental toxicants, owing to the anatomical and functional characteristics of the olfactory system, which allow inhaled toxicants to reach the central nervous system via the olfactory pathway. Experimental rodent models provide valuable tools for investigating the mechanisms underlying toxicant-induced olfactory injury under controlled conditions. In particular, intranasal vanadium exposure has emerged as a relevant experimental approach because it reproduces an environmentally relevant route of exposure while inducing pathological changes throughout the olfactory system. This review integrates current knowledge derived from experimental rodent models of intranasal vanadium exposure, covering the anatomy and physiology of the olfactory system, intranasal delivery strategies, the cellular and molecular mechanisms underlying vanadium-induced injury, and the associated histopathological, biochemical, behavioural and functional alterations. Vanadium-induced injury is characterized by oxidative stress, mitochondrial dysfunction, neuroinflammation, dysregulation of intracellular signalling pathways, and neuronal degeneration, leading to structural and functional alterations throughout the olfactory pathway. Finally, the review identifies current knowledge gaps regarding olfactory epithelial regeneration and functional recovery following toxic injury and highlights priorities for future research to improve experimental models of environmentally induced olfactory dysfunction.