title: Behavioral, neurochemical, and electrophysiological changes in an early spontaneous mouse model of nigrostriatal degeneration.
abstract: In idiopathic Parkinson's disease, clinical symptoms do not emerge until consistent neurodegeneration has occurred. The late appearance of symptoms implies the existence of a relatively long preclinical period during which several disease-induced neurochemical changes take place to mask the existence of the disease and delay its clinical manifestations. The aim of this study was to examine the neurochemical, neurophysiological, and behavioral changes induced by the loss of nigrostriatal innervation in the En1+/-;En2-/- mouse, in the 10 months following degeneration, compared to En2 null mutant mice. Behavioral analysis (Pole-test, Beam-walking test, and Inverted grid test) and field potential recordings in the striatum indicated that loss of ~70% of nigrostriatal neurons produced no significant functional effects until 8 months of age, when En1+/-;En2-/- animals started to show frank motor deficits and electrophysiological alterations in corticostriatal plasticity. Similarly, alterations in dopamine homeostasis, dopamine turnover, and dopamine innervation were observed in aged animals compared to young En1+/-;En2-/- mice. These data suggests that in En1+/-;En2-/- mice nigrostriatal degeneration in the substantia nigra is functionally compensated.
authors.affiliation: Department of Neuroscience, Section of Pharmacology, University of Pisa, Pisa, Italy. sgado@science.unitn.it
authors.forename: Paola
authors.initials: P
authors.lastname: Sgadò
authors.forename: Cristina
authors.initials: C
authors.lastname: Viaggi
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pinna
authors.forename: Cristina
authors.initials: C
authors.lastname: Marrone
authors.forename: Francesca
authors.initials: F
authors.lastname: Vaglini
authors.forename: Silvia
authors.initials: S
authors.lastname: Pontis
authors.forename: Nicola Biagio
authors.initials: NB
authors.lastname: Mercuri
authors.forename: Micaela
authors.initials: M
authors.lastname: Morelli
authors.forename: Giovanni Umberto
authors.initials: GU
authors.lastname: Corsini
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001923:Brain Chemistry / Q000235:genetics; D003342:Corpus Striatum / Q000473:pathology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005071:Evoked Potentials / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation / Q000235:genetics; D018737:Hand Strength / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics; D006719:Homovanillic Acid / Q000378:metabolism; D018476:Hypokinesia / Q000209:etiology; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000172:deficiency; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology*; D011597:Psychomotor Performance / Q000502:physiology; D013378:Substantia Nigra / Q000473:pathology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D000099266:Engrailed 2 Protein
chemical_list: D015102:3,4-Dihydroxyphenylacetic Acid; D004298:Dopamine; D050483:Dopamine Plasma Membrane Transport Proteins; D018398:Homeodomain Proteins; D006719:Homovanillic Acid; D009419:Nerve Tissue Proteins; D014446:Tyrosine 3-Monooxygenase; D000099266:Engrailed 2 Protein; C080330:En1 protein, mouse