Elsevier

Neuroscience

Volume 132, Issue 3, 2005, Pages 741-754
Neuroscience

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

https://doi.org/10.1016/j.neuroscience.2005.01.007Get rights and content

Abstract

Dendritic spines are important structures which receive synaptic inputs in many regions of the CNS. The goal of this study was to test the hypothesis that numbers of dendritic spines are significantly reduced on spiny neurones in basal ganglia regions in Parkinson’s disease as we had shown them to be in a rat model of the disease [Exp Brain Res 93 (1993) 17]. Postmortem tissue from the caudate and putamen of patients suffering from Parkinson’s disease was compared with that from people of a similar age who had no neurological damage. The morphology of Golgi-impregnated projection neurones (medium-sized spiny neurones) was examined quantitatively. The numerical density of dendritic spines on dendrites was reduced by about 27% in both nuclei. The size of the dendritic trees of these neurones was also significantly reduced in the caudate nucleus from the brains of PD cases and their complexity was changed in both the caudate nucleus and the putamen. Dendritic spines receive crucial excitatory input from the cerebral cortex. Reduction in both the density of spines and the total length of the remaining dendrites is likely to have a grave impact on the ability of these neurones to function normally and may partly explain the symptoms of the disorder.

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).

References (78)

  • O. Hornykiewicz

    Chemical neuroanatomy of the basal ganglianormal and in Parkinson’s disease

    J Chem Neuroanat

    (2001)
  • C.A. Ingham et al.

    Spine density on neostriatal neurons changes with 6-hydroxydopamine lesions and with age

    Brain Res

    (1989)
  • P.N. Izzo et al.

    Characterization of substance P- and [met]enkephalin- immunoreactive neurons in the caudate nucleus of cat and ferret by a single section Golgi procedure

    Neuroscience

    (1987)
  • M.S. Levine et al.

    Quantitative morphology of medium-size caudate spiny neurons in aged cats

    Neurobiol Aging

    (1986)
  • C. Marin et al.

    MK-801 prevents levodopa-induced motor response alterations in parkinsonian rats

    Brain Res

    (1996)
  • T.H. McNeill et al.

    Atrophy of medium spiny I striatal dendrites in advanced Parkinson’s disease

    Brain Res

    (1988)
  • C.K. Meshul et al.

    Time-dependent changes in striatal glutamate synapses following a 6-hydroxydopamine lesion

    Neuroscience

    (1999)
  • I.J. Mitchell et al.

    Reversal of parkinsonian symptoms in primates by antagonism of excitatory amino acid transmissionpotential mechanisms of action

    Neurosci Biobehav Rev

    (1997)
  • I.J. Mitchell et al.

    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

    Neuroscience

    (1989)
  • J.E. Nash et al.

    Antiparkinsonian actions of blockade of NR2B-containing NMDA receptors in the reserpine-treated rat

    Exp Neurol

    (1999)
  • S. Norton et al.

    A Golgi analysis of caudate neurons in rats exposed to carbon monoxide

    Brain Res

    (1977)
  • M.L. Schwartz et al.

    Long-lasting behavioral and dendritic spine deficits in the monocularly deprived albino rat

    Exp Neurol

    (1980)
  • M.G. Stewart et al.

    Re-structuring of synapses 24 hours after induction of long-term potentiation in the dentate gyrus of the rat hippocampus in vivo

    Neuroscience

    (2000)
  • H.B.M. Uylings et al.

    The metric analysis of three-dimensional dendritic tree patternsa methodological review

    J Neurosci Methods

    (1986)
  • A.M. Adinolfi

    The fine structure of neurons and synapses in the entopeduncular nucleus of the cat

    J Comp Neurol

    (1969)
  • G.W. Arbuthnott et al.

    Dopamine and synaptic plasticity in the neostriatum

    J Anat

    (2000)
  • J. Biernaskie et al.

    Enriched rehabilitative training promotes improved forelimb motor function and enhanced dendritic growth after focal ischemic injury

    J Neurosci

    (2001)
  • J.P. Bolam et al.

    Synaptic organisation of the basal ganglia

    J Anat

    (2000)
  • J.P. Bolam et al.

    Combined morphological and histochemical techniques for the study of neuronal microcircuits

  • H. Braak et al.

    Neuronal types in the striatum of man

    Cell Tiss Res

    (1982)
  • D. Brown et al.

    Early loss of dendritic spines in murine scrapie revealed by confocal analysis

    Neuroreport

    (2001)
  • G.K. Bryan et al.

    Deprived somatosensory-motor experience in stumptailed monkey neocortexdendritic spine density and dendritic branching of layer IIIB pyramidal cells

    J Comp Neurol

    (1989)
  • M. Carlsson et al.

    The NMDA antagonist MK-801 causes marked locomotor stimulation in monoamine-depleted mice

    J Neural Transm

    (1989)
  • J.C. Fiala et al.

    Dendrite structure

  • A. Globus et al.

    Effects of differential experience on dendritic spine counts in rat cerebral cortex

    J Comp Physiol Psychol

    (1973)
  • E. Gould et al.

    Gonadal steroids regulate dendritic spine density in hippocampal pyramidal cells in adulthood

    J Neurosci

    (1990)
  • G.A. Graveland et al.

    A Golgi study of the human neostriatumneurons and afferent fibers

    J Comp Neurol

    (1985)
  • J.T. Greenamyre et al.

    Antiparkinsonian effects of remacemide hydrochloride, a glutamate antagonist, in rodent and primate models of Parkinson’s disease

    Ann Neurol

    (1994)
  • J.T. Greenamyre et al.

    N-methyl-d-aspartate antagonists in the treatment of Parkinson’s disease

    Arch Neurol

    (1991)
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