TY - JOUR
T1 - Behavioral, neurochemical, and electrophysiological changes in an early spontaneous mouse model of nigrostriatal degeneration
AU - Sgadò, Paola
AU - Viaggi, Cristina
AU - Pinna, Annalisa
AU - Marrone, Cristina
AU - Vaglini, Francesca
AU - Pontis, Silvia
AU - Mercuri, Nicola Biagio
AU - Morelli, Micaela
AU - Corsini, Giovanni Umberto
PY - 2011/8
Y1 - 2011/8
N2 - 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.
AB - 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.
KW - Dopamine transporter
KW - Engrailed
KW - Parkinson's disease
KW - Presymptomatic compensation
UR - http://www.scopus.com/inward/record.url?scp=80052634167&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80052634167&partnerID=8YFLogxK
U2 - 10.1007/s12640-010-9232-9
DO - 10.1007/s12640-010-9232-9
M3 - Article
C2 - 21104462
AN - SCOPUS:80052634167
VL - 20
SP - 170
EP - 181
JO - Neurotoxicity Research
JF - Neurotoxicity Research
SN - 1029-8428
IS - 2
ER -