Striatal 6-OHDA lesion in mice: Investigating early neurochemical changes underlying Parkinson's disease.
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.
Branchi
Igor
I
Section of Behavioural Neurosciences, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, 00161 Rome, Italy. igor.branchi@iss.it
D'Andrea
Ivana
I
Armida
Monica
M
Carnevale
Daniela
D
Ajmone-Cat
Maria Antonietta
MA
Pèzzola
Antonella
A
Potenza
Rosa Luisa
RL
Morgese
Maria Grazia
MG
Cassano
Tommaso
T
Minghetti
Luisa
L
Popoli
Patrizia
P
Alleva
Enrico
E
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
D018663:Adrenergic Agents; D015306:Biogenic Monoamines; D019208:Brain-Derived Neurotrophic Factor; C075750:8-epi-prostaglandin F2alpha; D016627:Oxidopamine; D015237:Dinoprost; D015232:Dinoprostone