Seasonal changes in brain serotonin transporter binding in short 5-HTTLPR-allele carriers but not in long-allele homozygotes

Several findings suggest seasonal variations in the serotonin (5-HT) system. We sought evidence for seasonal variation in the serotonin transporter (5-HTT). We found that length of daylight time in minutes correlates negatively with 5-HTT binding in the putamen and the caudate, with a similar tendency in the thalamus, but no such association in the midbrain. In the putamen, an anatomical region with a dense serotonin innervation that is implicated in processing of aversive stimuli, we found a significant gene*daylight effect with a negative correlation between the 5-HTT binding and daylight time in carriers of the short 5-HTTLPR allele, but not in carriers of the long allele. The neurobiological endophenotype identified here directly links activation studies, showing responses on the neural circuit level, with dynamic changes in transporter expression measured in vivo

A Comprehensive Approach to Off-line Advanced Error Troubleshooting in Intelligent Manufacturing Systems

The errors recovery in the production systems will be always an open issue. Therefore, the FMSs have to be endowed with tools and techniques allowing an automatic recovery of errors. The objective of this work consists in proposing an off-line version of the software framework for error troubleshooting in a flexible manufacturing system [1]. The main difference between the on-line and off-line version is that the error database is stored on the mobile device and the frame marker device is connected directly to the FMS components without the need of the PC.). Our framework system is designed to solve the failures in the functioning of the FMS and to generate self-training from previous experience

High brain serotonin levels in migraine between attacks:A 5-HT₄ receptor binding PET study

Migraine has been hypothesized to be a syndrome of chronic low serotonin (5-HT) levels, but investigations of brain 5-HT levels have given equivocal results. Here, we used positron emission tomography (PET) imaging of the 5-HT4 receptor as a proxy for brain 5-HT levels. Given that the 5-HT4 receptor is inversely related to brain 5-HT levels, we hypothesized that between attacks migraine patients would have higher 5-HT4 receptor binding compared to controls. Eighteen migraine patients without aura (migraine free >48 h), and 16 age- and sex-matched controls underwent PET scans after injection of [11C]SB207145, a specific 5-HT4 receptor radioligand. An investigator blinded to group calculated a neocortical mean [11C]SB207145 binding potential (BPND). Three migraine patients reported a migraine attack within 48 h after the scan and were excluded from the primary analysis. Comparing 15 migraine patients and 16 controls, we found that migraine patients have significantly lower neocortical 5-HT4 receptor binding than controls (0.60 ± 0.09 vs. 0.67 ± 0.05, p = .024), corrected for 5-HTTLPR genotype, sex and age. We found no association between 5-HT4 receptor binding and attack frequency, years with migraine or time since last migraine attack. Our finding of lower 5-HT4 receptor binding in migraine patients is suggestive of higher brain 5-HT levels. This is in contrast with the current belief that migraine is associated with low brain 5-HT levels. High brain 5-HT levels may represent a trait of the migraine brain or it could be a consequence of migraine attacks. Keywords: Headache, Pain, Neuroimaging, Brain, Serotonergic mechanism

Measuring endogenous changes in serotonergic neurotransmission with [11C]Cimbi-36 positron emission tomography in humans

Abstract Developing positron emission tomography (PET) radioligands for the detection of endogenous serotonin release will enable the investigation of serotonergic deficits in many neuropsychiatric disorders. The present study investigates how acute challenges that aim to increase or decrease cerebral serotonin levels affect binding of the serotonin 2A receptor (5-HT2AR) agonist radioligand [11C]Cimbi-36. In a randomized, double-blind, placebo-controlled, three-arm design, 23 healthy volunteers were PET scanned twice with [11C]Cimbi-36: at baseline and following double-blind assignment to one of three interventions (1) infusion of the selective serotonin reuptake inhibitor (SSRI) citalopram preceded by oral dosing of the 5-HT1AR antagonist pindolol, (n = 8) (2) acute tryptophan depletion (ATD) (n = 7) and (3) placebo (n = 8). Two-sample t-tests revealed no significant group differences in percent change of neocortical [11C]Cimbi-36 binding from baseline to intervention between placebo and citalopram/pindolol (p = 0.4) or between placebo and ATD (p = 0.5). Notably, there was a significantly larger within-group variation in 5-HT2AR binding after intervention with citalopram/pindolol, as compared with placebo (p = 0.007). These findings suggest that neither ATD nor a combination of citalopram and pindolol elicit acute unidirectional changes in serotonin levels sufficient to be detected with [11C]Cimbi-36 PET in neocortex. We suggest that the large interindividual variation in 5-HT2AR binding after citalopram/pindolol reflects that after an acute SSRI intervention, individuals respond substantially different in terms of their brain serotonin levels. Our observation has a potential impact for the understanding of patient responses to SSRI

Fluor-18 jelzett adenozin-receptor ligandok szintézise

This thesis presents a study of introduction of fluorine-18, a positron-emitting radioisotope to the designed position of molecules of adenosine type. This thesis also includes strategies of synthesising of precursors, into which the fluorine-18 isotope, either in fluoride ion form or as a suitable fluorine-containing small molecule, can be introduced. The synthesized labelled molecules make the investigation of adenosine-receptors by PET technique possible. Preliminary biological evaluation of one of these molecules, namely 5’-N-(2-[18F]fluoroethyl)-carboxamidoadenosine is also presented. Two molecules were chosen to synthesise their fluorine-18 labelled forms: 5’-deoxy-5’-fluoro-adenosine and 5’-N-(2-fluoroethyl)-carboxamidoadenosine. Both compounds were labelled in two ways, each synthetic route includes nucleophilic fluorination with [18F]fluoride ion. 5’-Deoxy-5’-[18F]fluoro-adenosine would serve as a suitable model-compound for the synthesis of fluorine-18 labelled ligands; the appropriate modification of the adenine moiety leads to increased selectivity towards the chosen receptor subtype. As the radiochemical yields proved to be rather low, using either 5’-deoxy-5’-haloadenosines or N6-benzoyl 2’,3’-isopropylideneadenosine-5’-sulfonates as precursors, we had to resign to label adenosine at that (5’) position. Although N6-benzoyl 2’,3’-isopropylideneadenosine-5’-tosylate, one of these sulfonates was not proven to be a suitable precursor in the radiofluorination reactions, it served as an appropriate starting material in radioiodination reactions. 5’-N-(2-fluoroethyl)-carboxamidoadenosine ([18F]FNECA), as a fluorine-18 labelled analogue of NECA represents a PET isotope labelled agonist with given adenosine receptor specificity. It was synthesised in the following ways: in the reaction of [18F]fluoride with 5’-N,N-ethylene-2’,3’-O-isopropylidenecarboxamido-adenosine as well as by reacting 2-[18F]fluoroethylamine with 2’,3’-O-isopropylideneadenosine-5’-uronic acid. This latter route provides sufficient [18F]FNECA for the subsequent preliminary biological evaluation using PET-technique. According to the preliminary biological evaluation, agonist [18F]FNECA labelled with positron emitting isotope is capable of mapping the distribution for adenosine-receptors of P1 type, as well as investigating of receptor-regulation processes in vivo.Ph.D. Thesis ; Positron Emission Tomograph Centre, University of Debrecen, Medical and Health Science Center, 2002Ph