Neural mechanisms underlying parkinsonian symptoms based upon regional uptake of 2-deoxyglucose in monkeys exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

doi:10.1016/0306-4522(89)90120-6

Neuroscience

Volume 32, Issue 1, 1989, Pages 213-226

https://doi.org/10.1016/0306-4522(89)90120-6 Get rights and content

Abstract

The 2-deoxyglucose metabolic mapping technique has been used to investigate the neural mechanisms which underlie the symptoms of Parkinsonism in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine primate model of Parkinson's disease. In six cynomolgus monkeys, l-methyl-4-phenyl-1,2,3,6tetrahydropyridine was either (a) administered intravenously to induce generalized Parkinsonism, or (b) infused into one carotid artery to induce unilateral Parkinsonism.Post-mortem examination revealed profound cell loss from the substantia nigra, pars compacta either bilaterally or unilaterally in the two groups, respectively. In addition, there was pathological involvement of the ventral tegmental area and locus coeruleus in animals receiving intravenous 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

2-Deoxyglucose autoradiography revealed widespread changes in 2-deoxyglucose uptake in the brains of parkinsonian animals when compared to controls. Most of these changes were in basal ganglia and related structures and were qualitatively similar in the two groups of experimental animals. Prominent increases in 2-deoxyglucose uptake were observed in the lateral segment of the globus pallidus (24–27%), the ventral anterior and ventral lateral nuclei of the thalamus (14–22%) and the nucleus tegmenti pedunculopontinus of the caudal midbrain (17–69%). A profound decrease (17–26%) in 2-deoxyglucose uptake was observed in the subthalamic nucleus.

We propose these data to indicate that in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism there is the following pattern of abnormal neuronal activity in basal ganglia circuitry: (i) increased activity in the projection from the putamen to the lateral segment of the globus pallidus; (ii) decreased activity in the projection from the putamen to the medial segment of the globus pallidus; (iii) decreased activity in the projection from the lateral segment of the globus pallidus to the subthalamic nucleus; (iv) increased activity in the projection from the subthalamic nucleus to the globus pallidus; and (v) increased activity in neurons of the medial segment of the globus pallidus projecting to the ventral anterior/ventral lateral thalamus and the pedunculopontine nucleus.

These results are compared to the 2-deoxyglucose uptake findings in previous studies from this laboratory in hemiballism and hemichorea in the monkey. The central importance of the subthalamic nucleus in all three conditions is proposed, and supportive evidence for the excitatory nature of subthalamic efferent fibres is adduced.

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Neural mechanisms underlying parkinsonian symptoms based upon regional uptake of 2-deoxyglucose in monkeys exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Abstract

Life Sci.

Brain Res.

Neuroscience

Neuropharmacology

Neurosci. Lett.

Brain Res.

Brain Res.

Brain Res. Rev.

Neuroscience

Neurosci. Lett.

Brain Res.

Neurosci. Lett.

Brain Res.

Neurosci. Lett.

Brain Res.

Brain Res.

Brain Res.

Brain Res.

Brain Res.

Subthalamotomy in treatment of Parkinsonian tremor

J. Neurosurg.

Statistical Methods in Medical Research

Apparent discrepancy between single-unit activity and [14C]deoxyglucose labelling in optic tectum of the rattlesnake

J. Neurophysiol.

A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of substantia nigra byN-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine

The neurotoxicity of 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine in the monkey and man

Can. J. Neurol. Sci.

Apparent discrepancy between single-unit activity and [¹⁴C]deoxyglucose labelling in optic tectum of the rattlesnake