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José Luis LanciegoMETABOLIC ACTIVITY OF THE THALAMOSTRIATAL PATHWAY IN UNILATERALLY DOPAMINE-DEPLETED RATS.

Abstract :


T
he position of the caudal intralaminar nuclei within basal ganglia circuitry has largely been neglected in most studies dealing with basal ganglia function. During the past few years, there is a growing body of evidence sustaining that the thalamic parafascicular nucleus in rodents (PF) might exert a multifaceted modulation of basal ganglia nuclei, at different levels. Indeed, a primary non-dopaminergic neurodegeneration was observed in brains coming from patients suffering from Parkinson’s disease.
Our purpose was to study the metabolic status of the thalamostriatal pathway in rats with unilateral dopaminergic depletion. The experimental approach firstly comprises the unilateral 6-OHDA delivery in the medial forebrain bundle, followed by the measurement of the rotational behavior with apomorphine 30 days post-lesion. Animals showing a clear asymmetry (n = 25) were then subjected to bilateral delivery of the retrograde tracer Fluoro-Gold (FG) within mirror-like areas of the dorsolateral striatum. Next, the expression for vGLUT2 mRNA was detected by fluorescent, non-radioactive in situ hybridization within thalamostriatal-projecting neurons (retrogradely labeled with FG). Finally, PF areas containing FG-labeled neurons were dissected out by using the laser-guided microdissection microscope and the levels of vGLUT2 mRNA were measured by real-time PCR.
A marked neurodegeneration was found within the thalamostriatal pathway arising from PF on the side of the brain depleted with dopamine. Furthermore, PF neurons projecting to the dopamine-depleted striatum are highly hyperactive when compared to similar PF territories containing neurons projecting to a non-dopamine depleted striatum. Neurons projecting to the dopamine-depleted striatum showed a three-fold increase on the expression of vGLUT2 mRNA when compared to the neurons projecting to the striatum with normal dopamine content (p<0.001, according to the Wilcoxon test). This increased activity was only observed in the PF nucleus. Smaller increases found within the centrolateral and paracentral thalamic intralaminar nuclei failed to reach statistical significance.
In conclusion, the increased activity of the thalamostriatal pathway opens new vistas on the role to be played by the caudal intralaminar nuclei on the pathophysiology of Parkinson’s disease.

Supported by BFI2003-02033, Department of Education of the Government of Navarra and by the UTE-project/Foundation for Applied Medical Research.

Selected publications

Barroso-Chinea P, Cruz-Muros I, Aymerich MS, Rodriguez-Diaz M, Afonso-Oramas D, Lanciego JL, Gonzalez-Hernandez T.
Abstract Striatal expression of GDNF and differential vulnerability of midbrain dopaminergic cells.
Eur J Neurosci. 2005 Apr;21(7):1815-1827.
Castle M, Aymerich MS, Sanchez-Escobar C, Gonzalo N, Obeso JA, Lanciego JL.
Thalamic innervation of the direct and indirect basal ganglia pathways in the rat: Ipsi- and contralateral projections.
J Comp Neurol. 2005 Mar 7;483(2):143-53.
Lanciego JL, Gonzalo N, Rodriguez-Oroz MC, Rodriguez M, Obeso JA.
["Neurorestorative" cell therapy in Parkinson's disease: an unresolved debate]
An Sist Sanit Navar. 2004 Sep-Dec;27(3):299-304. Spanish.

Erwan Bézard