Does the Cerebrospinal Fluid Reflect Altered Redox State But Not Neurotrophic Support Loss in Parkinson's Disease?
Alteration in neurotrophic factors support and antioxidant defenses in the central nervous system (CNS) along with deficit of ferritin have been associated with idiopathic Parkinson's disease (PD). The objectives were to analyze in the cerebrospinal fluid (CSF) of patients with PD and controls the following: (i) the levels of the neuroprotectant factors glial cell line-derived neurotrophic factor, persephin, neurturin, and brain-derived neurotrophic factor, (ii) the levels of transforming growth factor-β1 (TGFβ1) and transforming growth factor-β2 (TGFβ2), proinflammatory factors, (iii) the activity of the antioxidant enzymes glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), catalase, superoxide dismutases (SODs), and peroxiredoxins (PRDxs), and (iv) ferritin levels. The study revealed that, among neurotrophic factors, only TGFβ1 levels were found to be enhanced in patients with PD (early, p < 0.05; advanced, p < 0.02). Regarding antioxidant enzymes, the activity of GPx, catalase, and PRDxs, all hydrogen peroxide scavengers, was found to be significantly reduced in patients (GPx, p < 0.001; catalase, p < 0.01; PRDxs, p < 0.01, one-way analysis of variance). Finally, ferritin content in CSF was significantly diminished over time in patients (early, p < 0.01, -49%; advanced, p < 0.001, -80.7%). Our observations lead to the hypothesis that parkinsonian patients suffer from a serious disturbance of redox state in the CNS, as evaluated through the CSF, characterized by reduced hydrogen peroxide scavenging and iron storage.
1 Laboratory of Neurophysiology and Molecular Neurology (BIO127), Department of Medical Physiology and Biophysics, University of Seville , Seville, Spain .|2 Department of Surgery, University of Seville and Department of Anesthesiology, Hospital Macarena, Seville, Spain .
Angel
A
Martín de Pablos
1 Laboratory of Neurophysiology and Molecular Neurology (BIO127), Department of Medical Physiology and Biophysics, University of Seville , Seville, Spain .|3 Neuroscience Clinical Unit & Asociación Neuroinvest, Hospital Macarena , Seville, Spain .
José-Manuel
JM
García-Moreno
1 Laboratory of Neurophysiology and Molecular Neurology (BIO127), Department of Medical Physiology and Biophysics, University of Seville , Seville, Spain .
Emilio
E
Fernández
D000368:Aged; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002374:Catalase / Q000134:cerebrospinal fluid; D005260:Female; D005293:Ferritins / Q000134:cerebrospinal fluid; D005979:Glutathione Peroxidase / Q000134:cerebrospinal fluid; D006801:Humans; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000134:cerebrospinal fluid*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000134:cerebrospinal fluid*; D054464:Peroxiredoxins / Q000134:cerebrospinal fluid; D013482:Superoxide Dismutase / Q000134:cerebrospinal fluid; D053773:Transforming Growth Factor beta1 / Q000134:cerebrospinal fluid
D015415:Biomarkers; D009414:Nerve Growth Factors; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D005293:Ferritins; D054464:Peroxiredoxins; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase