Characterization of long-term motor deficits in the 6-OHDA model of Parkinson's disease in the common marmoset

Research aimed at developing new therapies for Parkinson's disease (PD) critically depend on valid animal models of the disease that allows for repeated testing of motor disabilities over extended time periods. We here present an extensive characterization of a wide range of motor symptoms in the 6-OHDA marmoset model of PD when tested over several months. The severity of motor deficits was quantified in two ways: (i) through manual scoring protocols appropriately adapted to include species specific motor behavior and (ii) using automated quantitative motion tracking based on image processing of the digital video recordings. We show that the automated methods allow for rapid and reliable characterization of motor dysfunctions, thus complementing the manual scoring procedures, and that robust motor symptoms lasting for several months could be induced when using a two-stage neurotoxic lesioning procedure involving one hemisphere at a time. This non-human primate model of PD should therefore be well suited for long-term evaluation of novel therapies for treatment of PD.

[1]  J. Eberling,et al.  Preclinical models of Parkinson's disease. , 2003, Current protocols in toxicology.

[2]  Dr. Heinz Stephan,et al.  The Brain of the Common Marmoset (Callithrix jacchus) , 1980, Springer Berlin Heidelberg.

[3]  S Fahn,et al.  Committee. Unified Parkinson’s Disease Rating Scale. , 2001 .

[4]  P. Jenner,et al.  Dopamine, but Not Norepinephrine or Serotonin, Reuptake Inhibition Reverses Motor Deficits in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Treated Primates , 2002, Journal of Pharmacology and Experimental Therapeutics.

[5]  Gorjan Alagic,et al.  #p , 2019, Quantum information & computation.

[6]  Edgard Morya,et al.  Comprehensive Analysis of Tissue Preservation and Recording Quality from Chronic Multielectrode Implants , 2011, PloS one.

[7]  J. Brotchie,et al.  Reversal of parkinsonian symptoms by intrastriatal and systemic manipulations of excitatory amino acid and dopamine transmission in the bilateral 6‐OHDA lesioned marmoset , 1995, Behavioural pharmacology.

[8]  R. Ridley,et al.  Long-term consequences of human alpha-synuclein overexpression in the primate ventral midbrain. , 2007, Brain : a journal of neurology.

[9]  A. Smit,et al.  Two new test methods to quantify motor deficits in a marmoset model for Parkinson's disease , 2009, Behavioural Brain Research.

[10]  U. Ungerstedt,et al.  6-hydroxydopamine-induced degeneration of the nigrostriatal dopamine pathway: the turning syndrome. , 1976, Pharmacology & therapeutics. Part B: General & systematic pharmacology.

[11]  R. Siezen,et al.  others , 1999, Microbial Biotechnology.

[12]  G. G. Stokes.  "J." , 1890, The New Yale Book of Quotations.

[13]  H. Wikström,et al.  Motor effects of a dopamine stabilizer (GMC1111) in primate models of Parkinson and hemiparkinsonism. , 2003, European journal of pharmacology.

[14]  S B Dunnett,et al.  Behavioural analysis of unilateral monoamine depletion in the marmoset. , 1992, Brain : a journal of neurology.

[15]  R. Ridley,et al.  Sensorimotor deficits in a unilateral intrastriatal 6-OHDA partial lesion model of Parkinson’s disease in marmoset monkeys , 2003, Experimental Neurology.

[16]  W. Dauer,et al.  Parkinson's Disease Mechanisms and Models , 2003, Neuron.

[17]  Miguel A L Nicolelis,et al.  Spinal Cord Stimulation Restores Locomotion in Animal Models of Parkinson's Disease , 2009, Science.

[18]  G. Petzinger,et al.  The parkinsonian toxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP): a technical review of its utility and safety , 2001, Journal of neurochemistry.

[19]  A. Iriki,et al.  The common marmoset as a novel animal model system for biomedical and neuroscience research applications. , 2012, Seminars in fetal & neonatal medicine.

[20]  Andisheh Eslamboli.  Marmoset monkey models of Parkinson's disease: Which model, when and why? , 2005, Brain Research Bulletin.

[21]  A. Benabid,et al.  Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus , 1991, The Lancet.

[22]  M. L. Nicolelis,et al.  Restoration of locomotive function in Parkinson’s disease by spinal cord stimulation: mechanistic approach , 2010, The European journal of neuroscience.

[23]  Michael Petrides,et al.  The marmoset brain in stereotaxic coordinates , 2012 .

[24]  A. Benabid,et al.  Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease. , 1987, Applied neurophysiology.

[25]  I. Mitchell,et al.  Reversal of Parkinsonian symptoms in primates by antagonism of excitatory amino acid transmission: Potential mechanisms of action , 1997, Neuroscience & Biobehavioral Reviews.