Unbiased prediction of the degree of midbrain dopaminergic neuron loss in parkinsonian mice using behavioral parameters

KEIFMAN E; ESCANDE M; TARAVINI I; BELFORTE J; MURER MG

Córdoba

Congreso; XXIX Congreso Anual de la Sociedad Argentina de Investigación en Neurociencia; 2014

Sociedad Argentina de Investigación en Neurociencia

Parkinson?s disease is a neurodegenerative disorder in which nigrostriatal dopaminergic neuronsare vastly degenerated by the time diagnosis is reached. Here we explore how accurately behavioralparameters predict the degree of dopaminergic denervetion in 6-hydroydopamine (6-OHDA) treatedmice. Although some treated mice clearly show hemiparkinsonism, symptom severity is highly variableand some animals seem to perform like controls. We conducted an unbiased multivariate clusteranalysis over the following parameters: i.spontaneous turning asymmetry, maximum velocity and totaldistance travelled, from video-tracks obtained in an Open Field; ii.motor coordination in an acceleratingrotarod; iii.forelimb voluntary use in the cylinder test. As result we found two clusters, one constitutedby symptomatic 6-OHDA mice with 84±5% substantia nigra neurons loss. The other group contains amixed population of sham and asymptomatic 6-OHDA mice with a mild -yet significant- loss of nigralneurons. We consider that the latter 6-OHDA group models a pre-clinical stage of the disease. Furtheranalysis revealed a linear relationship between nigrostriatal degeneration and symptom severity,arguing against a biological threshold for symptom onset. Overall, the data show that subjects withsmall lesions may elude diagnosis despite extensive behavioral testing, due to individual variabilityand the limited sensitivity of diagnostic procedures, resembling clinical settings.