Brain-Derived Neurotrophic Factor (BDNF) and Serotonin Transporter (SERT) in Platelets of Patients with Mild Huntington’s Disease: Relationships with Social Cognition Symptoms

Abstract

Peripheral biological correlates of early-stage Huntington's disease (HD) are currently attracting much interest given their possible use as prognostic predictors of later neurodegeneration.Since deficits in social-cognition processing are present among the initial disease symptoms, aim of this work was to appraise, in blood platelets, Brain-Derived Neurotrophic Factor (BDNF) and serotonin (5-HT) transporter (SERT), two proteins involved in human adaptive behavior as potential biochemical correlates of such disabilities in mild-HD.Thirteen gene positive and symptomatic patients (9M/4W, HD-stage II, age> 40y) together 11 gender/age matched controls without a concurrent diagnosis of psychiatric disorders, underwent a blood test to determine BDNF storage and membrane-bound SERT in platelets by ELISA immune-enzyme and [ 3 H]-paroxetine ([ 3 H]-PAR) binding assays, respectively. Concomitantly, all subjects were examined through a battery of socio-cognitive and emotion recognition questionnaires.Results showed moderately increased intra-platelet BDNF amounts (+20-22%) in patients versus controls, whereas [ 3 H]-PAR binding parameters, maximum density (Bmax) and dissociation constant (KD), did not appreciably vary between the two groups. While patients displaying significantly reduced cognitive/emotion abilities, biochemical parameters and clinical features or psychosocial scores did not correlate each other, except for platelet BDNF and the illness duration, positively correlated, or for SERT KDs and angry voice recognition ability, negatively correlated in both controls and patients. Therefore, in this pilot investigation, platelet BDNF and SERT did not specifically underlie psychosocial deficits in stage II-HD. Higher platelet BDNF storage in patients showing lasting-mild symptoms would derive from compensatory mechanisms. Thus, supplementary investigations are warranted by also comparing patients in other illness's phases.

Kynurenine pathway and autism spectrum phenotypes: an investigation among adults with autism spectrum disorder and their first-degree relatives

“…Blood samples were collected in vacutainer tubes containing K 3 EDTA as anticoagulant or a clot activator for serum separation. The K 3 EDTA vacutainer tubes were centrifuged at 150 g for 15 minutes in order to separate the platelet rich plasma (PRP) from the other cellular elements 75 . Then the PRP samples were transferred in Falcon tubes and centrifuged again together with clot activator tubes at 1500 g for 15 minutes in order to obtain platelet poor plasma (PPP) and platelet pellet.…”

“…The K 3 EDTA vacutainer tubes were centrifuged at 150 g for 15 minutes in order to separate the platelet rich plasma (PRP) from the other cellular elements. 75 Then the PRP samples were transferred in Falcon tubes and centrifuged again together with clot activator tubes at 1500 g for 15 minutes in order to obtain platelet poor plasma (PPP) and platelet pellet. The clot activator tubes were instead centrifuged only one time, at 1500 g for 15 minutes, in order to obtain serum aliquots.…”

What, When and How to Measure—Peripheral Biomarkers in Therapy of Huntington’s Disease

“…However, in other studies, no differences in serum or plasma BDNF levels were found between HD patients and healthy individuals [97,98]. To make this even more contradictory, one of the recent reports indicates increased levels of BDNF in the platelets of HD patients [99]. In addition, overexpression of BDNF in a HD mouse brain was shown to ameliorate the HD phenotype [100], and the BDNF knockout animals showed consistent symptoms like HD transgenic mice [101].…”

Recent Advances on the Role of Brain-Derived Neurotrophic Factor (BDNF) in Neurodegenerative Diseases

“…However, inconsistent changes have been reported in the peripheral BDNF levels of Huntington’s disease patients. Huntington’s disease patients exhibited moderately increased intra-platelet BDNF levels and significantly reduced cognitive/emotional abilities, suggesting that platelet BDNF did not specifically underlie psychosocial deficits in stage II Huntington’s disease [ 103 ]. By contrast, BDNF levels were decreased in the saliva and plasma of Huntington’s disease patients compared to the control [ 104 , 105 ], although there was no correlation between the BDNF level and motor symptoms and cognitive impairment [ 105 ].…”