Session Title: Neurodevelopment and Neurodegeneration
Presentation Date: Friday, March 14 – Saturday, March 15, 2009
DOPAMINERGIC AND SEROTONINERGIC STRIATAL SYSTEMS ARE SIMILARLY ALTERED IN PARKINSON'S DISEASE AND HUNTINGTON'S CHOREA
C. Bedard1, M.-J. Wallman1, M. Parent2, A. Parent1
1Laval University, Anatomy and Physiology, Quebec, Canada, 2Montreal University, Montreal, Canada
Aims: In contrast to our vast knowledge of the dopaminergic (DA) dysfunction, little is known about the involvement of serotonin (5-HT) systems in neurodegenerative diseases affecting basal ganglia. This study aims at characterizing the status of the DA and 5-HT innervations of the striatum in Parkinson's (PD) and Huntington's (HD) diseases compared to age-matched controls.
Methods: An immunohistochemical study was undertaken with antibodies raised against tyrosine hydroxylase (TH) and serotonin transporter (SERT) as markers of DA and 5-HT neuronal profiles, respectively. Densities and patterns of DA and 5-HT innervations were determined by semi-quantitative analysis of coronal sections at pre-commissural, commissural and post-commissural levels of the human striatum.
Results: In both normal and pathological cases, the caudate nucleus contained a larger number of TH+ and SERT+ fibers than putamen and accumbens nucleus. In pathological specimens, a significant loss of TH+ fibers and axon varicosities was noted throughout the striatum of PD and HD patients, whereas the number of SERT+ fibers was increased in PD and HD striata compared to controls. Furthermore, a thin TH-positive zone lying along the ventricular border of caudate nucleus was much more intensely stained in HD than in controls.
Conclusions: Our findings indicate that DA and 5-HT innervations of human striatum are similarly affected in PD and HD, two neurodegenerative disorders characterized by opposite motor anomalies. The decrease in TH+ fibers and the increase in SERT+ fibers that occur in the two diseases support the existence of 5-HT mechanisms compensating for DA losses at striatal level.