Serotonin and neurodegeneration: a preliminary study of platelet serotonin transporter (SERT) in patients with Huntington's disease

Abstract

INTRODUCTION Huntington’s disease (HD) is a rare genetic disease caused by the abnormal expansion of the N-terminal polyglutamine site present in the huntingtin (Htt) protein. Mutant Htts enhance a neurodegenerative process characterized by the loss of striatal medium-sized spiny GABA neurons accompanied by severe psychiatric, cognitive and motor control disturbances. The prodromic phase of HD is defined by affective symptoms and, particularly, by depressive mood, albeit the neurobiology of this co-morbidity is unclear. Since serotonin (5-HT) levels are considered a depression biomarker and platelets a suitable peripheral model to apprise 5-HT re-uptake system, we aimed here at measuring the platelet 5-HT transporter (SERT) in HD. METHODS Platelet SERT was determined by means of [3H]paroxetine binding in 13 HD patients (9M, 4F) and 11 controls (8M, 3F) to obtain its maximal binding capacity, Bmax (fmol/mg) and dissociation constant, Kd (nM). All recruited subjects came from the Neurology Unit of the “St. Chiara” Hospital, Pisa University, after signing the informed consent approved by the institutional Ethics Committee. Subjects underwent a whole venous blood withdraw and subsequent neurological/psycho-emotional tests. Blood was then processed for separation of platelet membranes and binding studies. RESULTS The [3H]paroxetine Bmax was 1067 ± 119 fmol/mg in platelets of controls while resulting slightly but not significantly reduced in patients: 916 ± 70 fmol/mg. A weak, still not significant, increase in Kd was also obtained in HD, 0.18 ± 0.02 nM, vs. controls, 0.16 ± 0.03 nM, whilst reporting significant negative correlations between Kd, verbal emotions or perception of face expressions both in all subjects and patients. CONCLUSIONS This study shows, though not decisively, that platelet SERT affinity relays with emotional cognitive functions. This pushes us to enlarge subjects’recruitment and investigations also on platelet SERT number in HD vs. controls