IFIBIO HOUSSAY   25014
INSTITUTO DE FISIOLOGIA Y BIOFISICA BERNARDO HOUSSAY
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Unbiased prediction of the degree of midbrain dopaminergic neuron loss in parkinsonian mice using behavioral parameters.
Autor/es:
KEIFMAN E; ESCANDE MV; TARAVINI IRE; BELFORTE J; MURER MG
Lugar:
Huerta Grande
Reunión:
Congreso; XXIX Congreso Anual de la Sociedad Argentina de Investigación en Neurociencia; 2014
Institución organizadora:
Sociedad Argentina de Investigación en Neurociencia
Resumen:
P107.-Unbiased prediction of the degree of midbrain dopaminergic neuron loss in parkinsonian mice using behavioral parameters Ettel Keifman1°, Mariela Verónica Escande1°, Irene R.E. Taravini2°, Juan Emilio Belforte1°, Mario Gustavo Murer1° 1°Grupo de Neurociencias de Sistemas, IFIBIO Houssay, Facultad de Medicina, UBA; 2°Laboratorio de Parkinsonismo Experimental, ININFA, Facultad de Farmacia y Bioquímica, UBA ettel@keifman.com.ar Parkinson?s disease is a neurodegenerative disorder in which nigrostriatal dopaminergic neurons are vastly degenerated by the time diagnosis is reached. Here we explore how accurately behavioral parameters predict the degree of dopaminergic denervetion in 6-hydroydopamine (6-OHDA) treated mice. Although some treated mice clearly show hemiparkinsonism, symptom severity is highly variable and some animals seem to perform like controls. We conducted an unbiased multivariate cluster analysis over the following parameters: i.spontaneous turning asymmetry, maximum velocity and total distance travelled, from video-tracks obtained in an Open Field; ii.motor coordination in an accelerating rotarod; iii.forelimb voluntary use in the cylinder test. As result we found two clusters, one constituted by symptomatic 6-OHDA mice with 84±5% substantia nigra neurons loss. The other group contains a mixed population of sham and asymptomatic 6-OHDA mice with a mild -yet significant- loss of nigral neurons. We consider that the latter 6-OHDA group models a pre-clinical stage of the disease. Further analysis revealed a linear relationship between nigrostriatal degeneration and symptom severity, arguing against a biological threshold for symptom onset. Overall, the data show that subjects with small lesions may elude diagnosis despite extensive behavioral testing, due to individual variability and the limited sensitivity of diagnostic procedures, resembling clinical settings.