Evidence of a breakdown of corticostriatal connections in Parkinson’s disease
Section snippets
Subject population
Five controls (four females and one male) with no clinical or pathological features of neurological disease were studied (Table 1). Their ages ranged from 59 to 90 years (mean age, 78.2 years) with a PM delay (from death to fixation of the small samples) ranging from 14 to 24 h (mean PM delay, 20.6 h). Five idiopathic PD patients were studied (three males and two females) with ages ranging from 73 to 82 years (mean age, 77.4 years) and a PM delay ranging from 22.5 to 29 h (mean PM delay, 25.4
Results
The two Golgi methods used (block and section Golgi) produced similar levels of impregnation although sometimes the center of blocks was pale where the chemicals had not penetrated and these regions lacked impregnated neurons. Both methods were used for the analysis. Golgi-impregnated cells were generally scattered throughout the caudate and the putamen, sometimes being clumped into groups of neurones.
Discussion
This is the first study to our knowledge to demonstrate a significant loss of spines from medium-sized spiny neurones in both the caudate and putamen of the brains from PD patients collected PM. Our study has also identified a reduction in the extent of the dendritic tree in PD in the caudate as shown by several measurements (the length of the longest dendrite, the total dendritic length and the extent of the dendritic arbor). The number of dendritic branches of medium-sized spiny neurones was
Conclusions
This study set out to assess the spine density and dendritic morphology of medium-sized spiny neurones in the caudate and putamen nuclei of the basal ganglia in PD. The reduction of spine density and dendritic arbor is likely to cause changes in normal neural processing through the striatum and could even create the problems of movement initiation witnessed in PD. In agreement with the animal model data this human PM study suggests that the severe reduction of dopamine inputs to the caudate and
Acknowledgments
This project was funded by the Parkinson’s Disease Society (grants 4004 and 4012). Many thanks to Prof. Paul Bolam for helpful comments. Preliminary work was supported by the Wellcome Trust (grant 040197).
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