Olfactory bulb 6-OHDA neurotoxicity as a model of early cortical dysfunction

The olfactory bulb (OB) is one of the earliest brain regions affected in neurodegenerative diseases such as Parkinson's disease (PD). Its high metabolic rate, dopaminergic modulation, and connectivity with the cortical and limbic regions make it particularly vulnerable to early neuroinflammatory and oxidative processes. This study aimed to investigate whether the administration of 6-hydroxydopamine (6-OHDA) into the OB induces behavioral, redox, and inflammatory alterations associated with early cortical disturbances. Male Wistar rats were randomly assigned to the sham or 6-OHDA groups and underwent stereotaxic injection of the vehicle or 6-OHDA into the left OB. Behavioral performance was assessed in the open-field test 12 days after surgery, and cortical tissue was collected for biochemical and molecular analyses. Cytokines (IL-1β, IL-6, TNF-α, IL-10, IFN-γ, and MCP-1) were quantified by Luminex, redox parameters (CAT, GPx, MDA, and protein carbonyls) by spectrophotometry, and neuronal signaling proteins (c-FOS, CREB, and BDNF) by qPCR. Animals with 6-OHDA lesions exhibited decreased latency and increased time spent in the central zone of the open field, indicating altered exploratory behavior. IL-6 levels were significantly elevated, whereas IFN-γ was reduced in the cortex, while IL-1β, TNF-α, MCP-1, and IL-10 remained unchanged. The oxidative stress markers MDA and protein carbonyls were increased, while catalase and glutathione peroxidase activities showed no change. The expression of c-FOS, CREB, and BDNF was not significantly modified. These findings indicate that localized 6-OHDA administration in the OB is sufficient to elicit behavioral, inflammatory, and oxidative alterations in connected cortical regions, which may resemble early non-motor features associated with olfactory dysfunction, without representing a neurodegenerative disease-specific process.