Comparative Neutrophil Production of Nitric Oxide and Hydrogen Peroxide in Parkinson's and Alzheimer's Diseases

GATTO EM, CARRERAS MC, RIOBÓ N, PARGAMENT G, ALLEGRI R, PODEROSO JJ

Helsinki, Finlandia

Congreso; 7th Congress of European Federation of Neurological Societies; 2003

OBJECTIVE: To measure nitric oxide (NO) and hydrogen peroxide (H2O2) release by activated polymorphonuclear cells (PMN) from patients with Parkinson's (PD) or Alzheimer's disease (AD). BACKGROUND: Evidence is now compelling that NO is a mediator of neuronal damage in PD and AD. In accord, we recently reported an increased NO production rate and an overexpression of neuronal nitric oxide synthase (nNOS) in PMN from PD patients. On the other hand, NO has been implicated in the mechanisms of learning and memory. The presence of nitrotyrosine in neurofibrillary tangles and a decreased nNOS expression in frontal, visual and hippocampal cortex in AD propose NO as a contributing factor in AD. In accord,b-amyloid peptide induces NO production. METHODS: PMN were isolated by Ficoll-Hypaque centrifugation in 21 patients with PD, 7 with AD and 17 age and sex-matched controls. NO and H2O2 were determined after phorbol myristate acetate (PMA) or N-formyl-methionyl-leucyl-phenylalanine (fMLP) activation, by conversion of oxymyoglobin to metmyoglobin and a fluorometric technique, respectively. RESULTS: The production rate of NO by PMN activated with PMA was 61 and 57% greater in de novo and chronically l-dopa treated PD patients than in controls (0.74±0.08 and 0.72±0.05 vs. 0.46±0.04; p<0.05). However in AD,  differences in NO production were only detected after fMLP activation (0.25±0.02 vs. 0.39±0.05; p=0.013). The H2O2 production rate was increased in treated PD (1.20±0.10 vs. 0.77±0.05; p<0.05), while no differences were observed between AD and controls. CONCLUSIONS:  Our results showed a different signaling pathway for increased NO production by PMN in PD and AD. Although studies in peripheral tissues may partially reflect the events in CNS, it is likely that NO contribution to neurodegeneration implicates several regulatory mechanisms.