INTRODUCTION: Vanadium compounds are known to modulate cellular signaling and metabolic pathways, but their dose-dependent effects in the brain remain poorly characterized. In particular, little is known about how acute exposure to vanadium affects protein expression in the prefrontal cortex. This is vital because such changes may influence memory and mental health.

AIM(S): The aim of this study was to analyze the effects of a single exposure to vanadium at doses of 2 mg/kg and 20 mg/kg on proteomic changes in the prefrontal cortex (PFC) of C57BL/6J mice.

METHOD(S): C57Bl/6J mice were acutely injected with sodium orthovanadate dissolved in water at doses of 2 mg/kg (V2) and 20 mg/kg (V20) (i.p.). High-throughput proteomic analysis was used to detect changes in protein expression in the prefrontal cortex (pFc). The pFc was selected according to Paxinos and Franklin, 2001.

RESULTS: Compared to the vehicle group, 22 proteins were differentially regulated in the V2 group (e.g., Mrfap1, Pla2g4a, Slc30a3, and down-regulated Rragd) and 26 proteins in the V20 group (Fkbp1b, Calml3, Ighg2b). The low dose of V induced moderate changes in pFC proteins, influencing mainly mitochondrial metabolism, synaptic function, and post-transcriptional regulation. These changes suggest an adaptive response. In contrast, the high dose of V (20 mg/kg) induced a stronger, mainly regulatory profile involving mitochondrial function, proteostasis, cellular stress responses, and neuronal signaling - indicating an increased cellular demand for homeostasis maintenance.

CONCLUSIONS: Together, these findings demonstrate that vanadium treatment induces distinct, dose-dependent proteomic signatures. The changes range from subtle metabolic and neuronal modulation at low doses to extensive metabolic and stress-related remodeling at high doses. This study provides insight into the molecular mechanisms underlying the biological response to increasing vanadium intensity. It also highlights key pathways potentially involved in neuronal and metabolic regulation.

FINANCIAL SUPPORT: The study was conducted thanks to funding from the statutory funds of the Maj Institute of Pharmacology of the Polish Academy of Sciences.