title: Striatal 6-OHDA lesion in mice: Investigating early neurochemical changes underlying Parkinson's disease.
abstract: Early phases of Parkinson's disease (PD) are characterized by a mild reduction of dopamine (DA) in striatum and by emergence of psychiatric disturbances that precede overt motor symptoms. In order to characterize the neurochemical re-arrangements induced by such striatal impairment, we used a mouse model in which a low dose of 6-hydroxydopamine (6-OHDA) was bilaterally injected into the dorsal striatum. These mice showed a DA reduction of about 40% that remained stable up to 12 weeks after injection. This reduction was accompanied by changes in DA metabolite levels, such as HVA, transiently reduced at 4 weeks, and DOPAC, decreased at 12 weeks. No change in the 5-hydroxytryptamine (5-HT) levels was found but the 5-hydroxyindoleacetic acid (5-HIAA)/5-HT ratio was increased at 4 weeks. In addition, at the same time-point, the levels of 15-F(2t)-IsoP, an index of oxidative stress, and of PGE(2), a major product of cyclooxygenase-2, were decreased in different brain areas while BDNF levels were increased. These neurochemical changes were accompanied by altered behavioral responses concerning the emotional reactivity. Overall, the present findings suggest that a change of 5-HT metabolism and a modification of oxidative stress levels may play a role in the early PD degeneration phases.
authors.affiliation: Section of Behavioural Neurosciences, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, 00161 Rome, Italy. igor.branchi@iss.it
authors.forename: Igor
authors.initials: I
authors.lastname: Branchi
authors.forename: Ivana
authors.initials: I
authors.lastname: D'Andrea
authors.forename: Monica
authors.initials: M
authors.lastname: Armida
authors.forename: Daniela
authors.initials: D
authors.lastname: Carnevale
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Ajmone-Cat
authors.forename: Antonella
authors.initials: A
authors.lastname: Pèzzola
authors.forename: Rosa Luisa
authors.initials: RL
authors.lastname: Potenza
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Morgese
authors.forename: Tommaso
authors.initials: T
authors.lastname: Cassano
authors.forename: Luisa
authors.initials: L
authors.lastname: Minghetti
authors.forename: Patrizia
authors.initials: P
authors.lastname: Popoli
authors.forename: Enrico
authors.initials: E
authors.lastname: Alleva
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015306:Biogenic Monoamines / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D008124:Locomotion / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D016627:Oxidopamine / Q000633:toxicity*; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D013550:Swimming
chemical_list: D018663:Adrenergic Agents; D015306:Biogenic Monoamines; D019208:Brain-Derived Neurotrophic Factor; C075750:8-epi-prostaglandin F2alpha; D016627:Oxidopamine; D015237:Dinoprost; D015232:Dinoprostone