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Spinal cord metabolism of the 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine-treated monkey
Abstract:
Nine monkeys (Macaca fascicularis) were used in this study. Four monkeys were rendered parkinsonian by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) 0.5 mg/kg intravenously. Three animals were injected once daily for 4 days, and one animal once weekly for 4 weeks. Five animals were used as controls. All MPTP-treated animals demonstrated the same clinical features which included akinesia, bradykinesia, a flexed posture of the trunk and all extremities, decreased initiation of the threat response, decreased vocalization and difficulty in swallowing. An increase in rigidity and reflexes was noted in all extremities. Tremor was present in all animals. Determination of the local spinal metabolic rate of glucose (LSMRg) utilization revealed an increase (P less than 0.05) in LSMRg in Rexed layer I in all cord segments and in Rexed layer II in both cervical and lumbar segments. Rexed layer X demonstrated a significant (P less than 0.05) increase in LSMRg at the cervical cord. The LSMRg in the animal that received weekly injections was similar to the daily injected animals.
Insights
MPTP-induced parkinsonism in monkeys increased glucose metabolism in specific spinal cord layers. This finding suggests altered neural activity in the spinal cord during Parkinson
Area of Science:
- Neuroscience
- Primate Models
- Spinal Cord Physiology
Background:
- Parkinson's disease is a neurodegenerative disorder affecting motor control.
- 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin used to create parkinsonian models in animals.
- Spinal cord metabolic activity changes in neurological disorders are not fully understood.
Purpose of the Study:
- To investigate the effects of MPTP-induced parkinsonism on spinal cord glucose metabolism in Macaca fascicularis.
- To correlate clinical parkinsonian symptoms with changes in local spinal metabolic rate of glucose (LSMRg).
Main Methods:
- Four cynomolgus monkeys (Macaca fascicularis) were administered MPTP intravenously to induce parkinsonism.
- Control group consisted of five untreated monkeys.
- Local spinal metabolic rate of glucose (LSMRg) was determined across different Rexed laminae of the spinal cord.
Main Results:
- MPTP-treated monkeys exhibited classic parkinsonian symptoms including akinesia, bradykinesia, rigidity, and tremor.
- A significant increase in LSMRg was observed in Rexed layer I across all cord segments.
- Elevated LSMRg was also noted in Rexed layer II (cervical and lumbar) and Rexed layer X (cervical).
Conclusions:
- MPTP-induced parkinsonism in monkeys is associated with increased glucose metabolism in specific spinal cord dorsal and central gray matter regions.
- These findings highlight alterations in spinal cord neural activity secondary to parkinsonism.
- LSMRg changes may serve as a biomarker for neurodegeneration progression in the spinal cord.