Evidence of a breakdown of corticostriatal connections in Parkinson’s disease

Regional Volume Analysis of the Parkinson Disease Brain in Early Disease Stage: Gray Matter, White Matter, Striatum, and Thalamus

“…12 The cause of the loss of WM volume remains uncertain. Nevertheless, we assumed that a decreased dopaminergic tone, which results in a breakdown of corticostriatal connections 14 or impairment of various neurochemicals in broad areas, 33 may be 1 of the mechanisms involved in WM changes.…”

“…13 Significant loss of attenuation and length of the dendritic spines of medium-sized spiny neurons located in the striatum of patients with PD has been reported. 14 In addition, neuronal degeneration (40%-50%) has been observed in the intralaminar thalamic nuclei of PD brains, which is suggested to occur in early disease stages. 15,16 The major hypotheses of the present study were that a lack of brain atrophy in PD implies a low likelihood of detecting brain changes by using imaging analysis and that a high likelihood of detecting brain changes by using imaging means that overall, the brain atrophy is too developed to allow the differentiation of vulnerable areas; therefore, early changes in the most vulnerable brain regions constitute an ideal tool to discriminate variations in different brain structures.…”

“…The rationale for choosing these areas was that these structures play an important role in input and output pathways, respectively, in basal ganglia circuits and that loss of these structures reportedly represents an early disease period. [13][14][15][16] We also calculated the total volume of the GM and WM in whole brains of patients to evaluate structural changes that occur beyond the basal ganglia in early-stage PD.…”

Striatal plasticity and medium spiny neuron dendritic remodeling in parkinsonism

“…Both post-mortem studies of idiopathic PD and laboratory studies of animal models of parkinsonism have found that striatal dopamine depletion results in dystrophic changes in the dendrites of striatal MSNs [3,[6][7][8]. The morphological changes in MSNs include decreases in dendritic length, dendritic spine density, and total number of dendritic spines.…”

“…First, it is clear that dopamine depletion is the initiating event: MSN spine loss is seen in postmortem studies of PD, and in animals treated with 6-hydroxydopamine or reserpine to deplete striatal dopamine stores, as well as in animals in which dopamine signaling has been disrupted by chronic treatment with the D 2 receptor antagonist haloperidol [3,[6][7][8]10]. The latter finding, and the observation that MSNs of mice genetically lacking the D 2 dopamine receptor suffer from a loss of dendritic spines (unpublished observation), suggests that spine loss might be confined to MSNs that normally express the D 2 receptor.…”