title: Evidence of oxidative stress in the neocortex in incidental Lewy body disease.
abstract: Oxidative stress has been well documented in the substantia nigra in Parkinson disease (PD), but little is known about oxidative damage, particularly lipoxidation, advanced glycation (AGE), and AGE receptors (RAGE) in other structures, including the cerebral cortex, in early stages of diseases with Lewy bodies. The present study was undertaken to analyze these parameters in the frontal cortex (area 8), amygdala, and substantia nigra in selected cases with no neurologic symptoms and with neuropathologically verified incidental Lewy body disease-related changes, comparing them with healthy age-matched individuals. Results of the present study have shown mass spectrometric and immunologic evidences of increased lipoxidative damage by the markers malondialdehyde-lysine (MDAL) and 4-hydroxynonenal-lysine (HNE), increased expression of AGE in the substantia nigra, amygdala, and frontal cortex, and increased and heterogeneous RAGE cellular expression in the substantia nigra and frontal cortex in cases with early stages of parkinsonian neuropathology. In addition, increased content of the highly peroxidizable docosahexaenoic acid in the amygdala and frontal cortex. These changes were not associated to alpha-synuclein aggregation in cortex, contrasting with aggregates found in SDS-soluble fractions of frontal cortex in dementia with Lewy bodies (DLB) cases. The pattern of lipidic abnormalities differed in DLB and incidental Lewy body disease. Furthermore, although AGE and RAGE expression were raised in DLB, no increase in the total amount of HNE and MDAL adducts was found in the cerebral cortex in DLB. Preliminary analyses have identified 2 proteins with lipoxidative damage, alpha-synuclein and manganese superoxide dismutase (SOD2), in incidentally Lewy body disease cortex. This study demonstrates abnormal fatty acid profiles, increased and selective lipoxidative damage, and increased AGE and RAGE expression in the frontal cortex in cases with early stages of parkinsonian neuropathology without treatment. These findings further support antioxidant therapy in the treatment of PD to reduce cortical damage associated with oxidative stress.
authors.affiliation: Institut de Neuropatologia, Servei Anatomia Patològica, IDIBELL-Hospital Universitari de Bellvitge, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Dalfó
authors.forename: Manuel
authors.initials: M
authors.lastname: Portero-Otín
authors.forename: Victoria
authors.initials: V
authors.lastname: Ayala
authors.forename: Anna
authors.initials: A
authors.lastname: Martínez
authors.forename: Reinald
authors.initials: R
authors.lastname: Pamplona
authors.forename: Isidre
authors.initials: I
authors.lastname: Ferrer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000447:Aldehydes / Q000378:metabolism; D015153:Blotting, Western; D004281:Docosahexaenoic Acids / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D005227:Fatty Acids / Q000032:analysis / Q000378:metabolism; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D020961:Lewy Body Disease / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D013058:Mass Spectrometry; D019579:Neocortex / Q000378:metabolism / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D051843:Synucleins; D051844:alpha-Synuclein
chemical_list: D000447:Aldehydes; D005227:Fatty Acids; D017127:Glycation End Products, Advanced; D009419:Nerve Tissue Proteins; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D004281:Docosahexaenoic Acids; D008315:Malondialdehyde; C027576:4-hydroxy-2-nonenal