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Yoland Smith"Perte d'épines striatales dans la maladie de Parkinson: cause ou conséquence de la dégénérescence de la voie dopaminergique nigrostriatale ?"

Abstract :


Striatal spine loss is a well established pathology of Parkinson’s disease that can be induced in primate and nonhuman primate models of parkinsonism.
In this presentation, I will review evidence demonstrating this pathological feature and present data from our laboratory and others that show the high degree of regional specificity and the strong dependence of striatal spine pathology on striatal dopamine innervation. Data from MPTP-treated monkeys will be presented to demonstrate that spine loss is an early phenomenon that occurs prior to the development of movement disorders in parkinsonism. I will also provide evidence that this pathology affects both “direct and indirect” striatofugal pathways and largely correlates with the relative abundance of calcium binding proteins expression in striatal projection neurons. I will, then, present ultrastructural evidence for major changes in the synaptic microcircuitry of the two main axo-spinous glutamatergic afferents (ie the corticostriatal and thalamostriatal systems) to the striatum in Parkinson’s disease. Finally, I will conclude with a discussion of the potential relevance of spine plasticity in normal and pathological basal ganglia functions.
{Supported by National Institutes of Health and National Parkinson Foundation}
Using the MPTP-treated monkey model of parkinsonism we have The degree of spine loss in striatal medium spiny neurons (MSNs) has been correlated with progressive nigrostriatal dopaminergic denervation in the MPTP-treated monkey model of parkinsonism. Six control and six MPTP-treated monkeys were used. Spine density was determined in Golgi-impregnated MSNs from control, or from MPTP-treated monkeys with complete or partial striatal dopamine (DA) denervation. The progressive degeneration of tyrosine hydroxylase (TH) innervation was correlated with the degree of spine loss in the striatum of MPTP-treated monkeys. Quantitative electron microscopy immunocytochemistry for D1 receptor (D1) in the striatum of control and severely DA-depleted animals was performed. A significant (30-50%) reduction in spine density was found in both the caudate and putamen of severely DA-depleted striata; the sensorimotor post-commissural putamen being the most severely affected region for both dopamine denervation and spine loss. In partially DA-denervated striata, the extent of spine loss was tightly correlated with the degree of DA depletion. Both D1-immunoreactive and immunonegative spines were lost in the putamen of MPTP-treated monkeys. These data demonstrate that striatal spine loss in MPTP-treated monkeys is an early pathological event of parkinsonism, tightly correlated with the degree of nigrostriatal dopamine denervation that likely affects both direct and indirect striatofugal pathways.

Selected publications

Lanciego, JL, MC Rodriguez-Oroz, FJ Blesa, L Alvarez-Erviti, J Guridi, Y Smith and JA Obeso (2008) Lesion of the centromedian thalamic nucleus in MPTP-treated primates. Mov . Disorders (in press).
Grabowska, D, M Jayaraman, KM Kaltenbronn, SL Sandiford, Q Wang, S Jenkins, V Slepak, Y Smith and KJ Blumer (2008) Postnatal induction and localization of R7BP, a membrane-anchoring protein for RGS7 family-GBeta5 complexes in brain. Neuroscience (in press).
Rubio ME, KA Gudsnuk, Y Smith and DK Ryugo (2008) Revealing the molecular layer of the primate dorsal cochlear nucleus. Neuroscience (in press)
Mitrano, D, C. Arnold and Y Smith (2008) A comparative analysis of the subcellular and subsynaptic localization of group I mGluRs in the nucleus accumbens of normal and cocaine-treated rats. Neuroscience (in press)

Villalba R, H Lee and Y Smith (2008) Dopaminergic denervation and spine loss in the striatum of MPTP-treated monkeys. Exp. Neurol (in press).

Erwan Bézard