Olfactory Neuron Substance P is Overexpressed in Parkinson's Disease Reflecting Gut Dysfunction

Background, Objectives, Methods, Results, Conclusions Background: Substance P is a neuropeptide mostly expressed in the gastrointestinal-nervous ascending pathway in response to various noxious stimuli. Substance P might mediate detrimental neuroinflammatory events contributing to PD pathogenesis, although direct proofs are still lacking. Olfactory neurons well reflect central neuropathology, allowing dissecting molecular processes underlying the clinical-pathological dynamics of PD in vivo. Objective: To clarify the role of Substance P in PD through a molecular analysis of patients' olfactory neurons. Methods: Olfactory neurons were withdrawn in 30 patients and 20 sex/age-matched healthy controls by the mucosa brushing. Substance P and the NK1 receptor gene expression levels were comparatively measured by the Real Time-PCR; moreover, immunofluorescence staining to quantify Substance P was performed. In patients, biochemical data were correlated with main clinical scores, including the Gastrointestinal Dysfunction Scale for Parkinson's Disease and the presence of constipation. Results: In PD, olfactory neurons overexpressed Substance P. The expression was proportionally higher in patients with gastrointestinal dysfunction, including constipation. NK1 receptor levels, instead, did not differ between patients and controls. Conclusions: Substance P overexpression within olfactory neurons in association with gastrointestinal dysfunction reveals a main role for this tachykinin in PD pathogenesis. Substance P, indeed, might be a main mediator of the "body-first" trajectory, serving either as a specific biomarker or a novel therapeutic target.