Basal ganglia lesions after MPTP administration in rhesus monkeys

M.E. Emborg; J. Moirano; K.T. Schafernak; M. Moirano; M. Evans; T. Konecny; B. Roitberg; P. Ambarish; E. Mangubat; Y. Ma; D. Eidelberg; J. Holden; J.H. Kordower; J.E. Leestma

Neurobiology of Disease (Aug 2006)

Basal ganglia lesions after MPTP administration in rhesus monkeys

M.E. Emborg,
J. Moirano,
K.T. Schafernak,
M. Moirano,
M. Evans,
T. Konecny,
B. Roitberg,
P. Ambarish,
E. Mangubat,
Y. Ma,
D. Eidelberg,
J. Holden,
J.H. Kordower,
J.E. Leestma

Affiliations

M.E. Emborg: Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USA; Department of Anatomy, University of Wisconsin-Madison, Madison, WI 53715, USA; Corresponding author. Wisconsin National Primate Research Center, University of Wisconsin-Madison, 1223 Capitol Court, Madison, WI 53715, USA. Fax: +1 608 263 3500.
J. Moirano: Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USA; Department of Medical Physics, University of Wisconsin-Madison, Madison, WI 53715, USA
K.T. Schafernak: Department of Pathology, Northwestern University, Chicago, IL 60611, USA
M. Moirano: Department of Neurological Sciences, Rush University, Chicago, IL 60612, USA
M. Evans: Department of Neurological Sciences, Rush University, Chicago, IL 60612, USA
T. Konecny: Department of Neurosurgery, University of Illinois at Chicago, Chicago, IL 60612, USA
B. Roitberg: Department of Neurosurgery, University of Illinois at Chicago, Chicago, IL 60612, USA
P. Ambarish: Department of Bioengineering, University of Illinois at Chicago, Chicago, IL 60612, USA
E. Mangubat: Department of Neurosurgery, University of Illinois at Chicago, Chicago, IL 60612, USA
Y. Ma: Center for Neurosciences, Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY 11030, USA
D. Eidelberg: Center for Neurosciences, Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY 11030, USA
J. Holden: Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USA; Department of Medical Physics, University of Wisconsin-Madison, Madison, WI 53715, USA; Department of Radiology, University of Wisconsin-Madison, Madison, WI 53715, USA
J.H. Kordower: Department of Neurological Sciences, Rush University, Chicago, IL 60612, USA
J.E. Leestma: Department of Pathology, Children's Memorial Hospital, Chicago, IL 60611, USA

Journal volume & issue: Vol. 23, no. 2
pp. 281 – 289

Abstract

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In monkeys, intracarotid infusion of a single low dose of MPTP reliably induces a hemiparkinsonian syndrome that is stable over time. This model has been widely used to assess novel anti-parkinsonian therapies. Here, we report the exceptional finding of severe necrotic lesions that were observed in the basal ganglia (but not in the substantia nigra) of monkeys that received a single intracarotid injection of MPTP followed by gene therapy treatments. Although extensive unilateral dopaminergic nigrostriatal loss was found in all the animals, partial behavioral recovery was observed in the subjects that presented pallidal necrotic lesions. This report discusses possible causes and effects of the necrotic lesions and their locations and the value of the intracarotid MPTP model. Testing novel therapies in monkey models has become an essential step before clinical trials. These results indicate that evaluation of any treatment should consider possible confounding factors that may affect the results.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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