Delayed onset of progressive dystonia following subacute 3-nitropropionic acid treatment in Cebus apella monkeys.

Abstract

Delayed abnormal movements can be observed in patients with acute neurologic insult after a prolonged period of apparent neurologic stability. To reproduce such a secondary neurologic manifestation in primates, the present experiment investigated whether systemic administration of subacute 3-nitropropionic acid (3NP), a mitochondrial toxin, could induce abnormal movements that were delayed and progressive over time. Four Cebus apella monkeys received systemic 3NP injections until acute neurologic signs manifested. The monkeys were regularly video-recorded and rated for abnormal movements for up to 15 weeks after the cessation of 3NP treatment. Five to 6 weeks after the 3NP treatment, monkeys displayed a significant increase in dyskinesias compared with pretreatment conditions. Over time the chorea attenuated, whereas the dystonic movements increased in intensity and severity which was characterized by a delayed decrease of peak tangential velocity. The intensity of abnormal movements and extent of affected body regions observed in each monkey were consistent with the size of basal ganglia hypersignal as documented by T2 sequence on magnetic resonance imaging. Thus, more severe motor impairments were associated with large magnetic resonance image abnormalities. This novel primate model may be particularly useful for studying the structural changes underlying delayed and progressive manifestations of abnormal movements with the ultimate goal of facilitating the evaluation of novel therapeutic strategies.

• Authors: S Palfi, L Leventhal, C G Goetz, T Hantraye, B Z Roitberg, J Sramek, M Emborg, J H Kordower
• Journal: Movement disorders : official journal of the Movement Disorder Society (Mov Disord) Vol. 15 Issue 3 Pg. 524-30 (May 2000) ISSN: 0885-3185 [Print] United States
• PMID: 10830419 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Neurotoxins
• Nitro Compounds
• Propionates
• 3-nitropropionic acid

Topics

• Animals
• Basal Ganglia (drug effects)
• Brain Mapping
• Cebus
• Chorea (chemically induced, diagnosis)
• Dystonia (chemically induced, diagnosis)
• Mitochondria (drug effects)
• Neurotoxins (pharmacology)
• Nitro Compounds
• Parkinson Disease, Secondary (chemically induced, diagnosis)
• Propionates (pharmacology)