Uneven Pattern of Dopamine Loss in the Striatum of Patients with Idiopathic Parkinson's Disease

Abstract

Autografting of dopamine-producing adrenal medullary tissue to the striatal region of the brain is now being attempted in patients with Parkinson's disease. Since the success of this neurosurgical approach to dopamine-replacement therapy may depend on the selection of the most appropriate subregion of the striatum for implantation, we examined the pattern and degree of dopamine loss in striatum obtained at autopsy from eight patients with idiopathic Parkinson's disease. We found that in the putamen there was a nearly complete depletion of dopamine in all subdivisions, with the greatest reduction in the caudal portions (less than 1 percent of the dopamine remaining). In the caudate nucleus, the only subdivision with severe dopamine reduction was the most dorsal rostral part (4 percent of the dopamine remaining); the other subdivisions still had substantial levels of dopamine (up to approximately 40 percent of control levels). We propose that the motor deficits that are a constant and characteristic feature of idiopathic Parkinson's disease are for the most part a consequence of dopamine loss in the putamen, and that the dopamine-related caudate deficits (in "higher" cognitive functions) are, if present, less marked or restricted to discrete functions only. We conclude that the putamen--particularly its caudal portions--may be the most appropriate site for intrastriatal application of dopamine-producing autografts in patients with idiopathic Parkinson's disease.

The acute brain response to levodopa heralds dyskinesias in Parkinson disease

“…This part of the basal ganglia is most strongly affected by dopaminergic denervation in PD28 and is thought to play a central role in the pathophysiology of dyskinesias 23. Hypersensitivity of striatal medium spiny neurons to pulsatile dopamine receptor stimulation during task‐related corticostriatal activation of glutamate receptors has been identified as a key alteration in animal models of LID 8.…”

L-DOPA Disrupts Activity in the Nucleus Accumbens during Reversal Learning in Parkinson's Disease

“…Mild PD patients are impaired on probabilistic reversal learning when they are ON, but not when they are OFF L-DOPA (Cools et al, 2001). It was proposed that this impairment was due to detrimental 'over-dosing' of the ventral striatum, which is relatively spared of DA loss in early-stage PD (Farley et al, 1977;Kish et al, 1988). In keeping with this prediction, the present observation confirms that L-DOPA interacts with the NAc, not the dorsal striatum during reversal learning.…”

“…PD is characterized by striatal DA depletion and is accompanied by cognitive deficits from the earliest disease stages (Owen et al, 1992). The DA depletion progresses from the dorsal to the ventral striatum, so that, in early PD, the dorsal striatum is severely depleted, but the ventral striatum is relatively intact (Farley et al, 1977;Kish et al, 1988). Hence, mild PD provides a unique model for assessing dopaminergic drug effects on neural systems with differential baseline DA levels.…”

Dopamine Cell Transplantation for Parkinson's Disease: The Importance of Controlled Clinical Trials

“…The issue is widely debated. Because the symptoms of Parkinson's disease develop only after a 50% loss of nigral neurons and a 60 to 80% reduction in striatal dopamine [57,58], complete replacement of dopamine-producing neurons may not be required to improve motor skills and to reduce the need for L-DOPA.…”