Attenuation effects on the kerma rates in air after cesium depositions on grasslands

Since the reactor accident of Chernobyl, cesium depth profiles and nuclide-specific kerma rates in air have been determined for various grassland sites in south Bavaria and in Ukraine. The sites are described by soil characteristics, annual precipitation, distance from release point, mode of deposition, and activity per unit area. The effects of surface roughness and migration of cesium into the soil on the kerma rate in air over grasslands was determined by two methods. The kerma rates in air obtained by the evaluations of in situ gamma-ray spectrometry results and of measured activity distributions in the soil showed only negligible differences for the observation period of 6 years after deposition. For the sites in Ukraine the kerma rate in air per activity per unit area was found to be systematically 40% higher than in Bavaria. The results from Bavaria on the attenuation of the kerma rate and a data set, including experiences from the weapons test fallout, are analytically approximated as a function of time up to 25 years after deposition.     

Human Platelet Sulfotransferase Shows Seasonal Rhythms

Our study aimed to investigate the possible presence of seasonal changes in platelet phenolsulfotransferase (ST) in a group of 20 healthy, drug-free subjects of both sexes and between 24 and 37 years of age. Blood samples were taken four times a year in the period immediately following the equinoxes and the solstices. The results showed that both STs underwent seasonal changes: the lowest values were found in autumn and in winter, and the highest in the summer. A positive correlation between the two STs and the length of the photoperiod was observed in winter, whereas in the spring we detected a negative correlation between the TL ST and the photoperiod length. Future studies should clarify whether platelet ST of patients with mood disorders shows a similar seasonality.     

1-Aminocyclopentane-1,2,4-tricarboxylic acids screening on glutamatergic and serotonergic systems

Enantiopure constrained 1-aminocyclopentane-1,2,4-tricarboxylic acids containing the glutamic acid skeleton were prepared as two diastereomers characterized by having the carboxylic groups in position two and four cis-oriented to each other and trans with respect to 1-carboxylic group and all cis-oriented carboxylic groups, respectively. A biochemical screening of activity of the above amino acids was investigated on glutamate and 5-HT receptors to find a possible metabotropic agonist, acting on the serotoninergic system.     

Distribution of Serotonin Receptor of Type 6 (5-HT6) in Human Brain Post-mortem. A Pharmacology, Autoradiography and Immunohistochemistry Study

The aim of this study was to investigate the distribution of serotonin (5-HT) receptors of type 6 (5-HT(6)) in postmortem human prefrontal cortex, striatum and hippocampus. The brain samples were obtained from 6 subjects who had died for causes not involving primarily or secondarily the CNS. The 5-HT(6) receptor distribution was explored by the [(125)I]SB-258585 binding to brain membranes followed by the pharmacological characterization, where possible, and by autoradiographic, immunohistochemical and immunofluorescence evaluations. A specific and saturable [(125)I]SB-258585 binding was detected in striatum only, with a pharmacological characterization consistent with that of a 5-HT(6) receptor. The autoradiography showed the presence of a specific [(125)I]SB-258585 binding distributed homogeneously in caudate, putamen and accumbens. The immunohistochemistry, carried out in the striatum only, coupled with the immunofluorescence with glial fibrillary acidic protein (GFAP) and parvalbumin (PV) showed the co-localization of 5-HT(6) receptor with PV, while indicating that this receptor subtype was expressed in neurons and not in astrocytes. Taken together, the present findings showed the presence of a higher density of 5-HT(6) receptors, as labeled by [(125)I]SB-258585, in striatum than in hippocampus and prefrontal cortex, and specifically within the neuronal body. In addition, they would suggest that striatum is one of the major potential CNS targets linked to 5-HT(6) receptor modulation.     

[3H]Ketanserin Binding in Human Brain Postmortem

This study aimed at comparing the binding characteristics of [³H]ketanserin, a high-affinity serotonin 2A (5-HT_2A) receptor antagonist, in the prefrontal cortex, hippocampus and striatum of human brain post-mortem. The results indicated the presence of a single population of binding sites in all the regions investigated, with no statistical difference in maximum binding capacity (B_max) or dissociation constant (K_d) values. The pharmacological profile of [³H]ketanserin binding was consistent with the labeling of the 5-HT_2A receptor, since it revealed a competing drug potency ranking of ketanserin = spiperone > clozapine = haloperidol > methysergide > mesulergine > 5-HT. In conclusion, the 5-HT_2A receptor, as labeled by [³H]ketanserin, would seem to consist of a homogenous population of binding sites and to be equally distributed in human prefronto-cortical, limbic and extrapyramidal structures.     

Human Serotonin Transporter Expression During Megakaryocytic Differentiation of MEG-01 Cells

The serotonin (5-HT) transporter (SERT) has been found altered in platelets of patients with genetically complex disorders, including mood-anxiety, pain and eating disorders. In this study, we used cell cultures of platelet precursors as models of investigation on mechanisms of SERT regulation: SERT expression was appraised during megakaryocytic differentiation of human megakaryoblastic MEG-01 cells. Cells were cultured for 8 days with 10^?7M 4-β-12-tetradecanoylphorbol-13-acetate (β-TPA) in the presence of 10% fetal bovine serum (FBS) and SERT was assessed by real time PCR, immunofluorescence microscopy, Western blot and [³H]5-HT re-uptake. Results revealed that SERT is present in control-untreated MEG-01 cells. β-TPA-differentiating MEG-01 cells showed a redistribution of SERT fluorescence, diffuse to cell bodies and blebs along with a 3-fold SERT mRNA increase and a moderate raise in SERT protein (1.5/1.4-fold) by immunoblot and re-uptake assays. In summary, we have shown herein that control megakaryoblasts express the SERT protein. SERT is modulated by differentiation events, implying that SERT density in platelets is under the control of megakaryocytopoiesis stages. Differentiation of MEG-01 cells can provide considerable insight into interactions between SERT genetics, transmitter-hormonal/homeostatic mechanisms and signaling pathways.     

Serotonin receptor of type 6 (5-HT6) in human prefrontal cortex and hippocampus post-mortem: An immunohistochemical and immunofluorescence study

Given the paucity of data on the distribution of serotonin (5-HT) receptors of type 6 (5-HT₆) in the human brain, the aim of this study was to investigate their distribution in postmortem human prefrontal cortex, striatum and hippocampus by either immunohistochemical or immunofluorescence techniques.     

Species Comparison of Adenosine Receptor Subtypes in Brain and Testis

We aimed at comparing the binding characteristics of adenosine A₁ and A_2A receptors (A₁Rs and A_2ARs) in high-expressing cerebral areas, the cortex and striatum respectively, of human, bovine and rat brain. Adenosine A₃ receptor (A₃R) binding was studied in rat and bovine testis. Results confirmed species differences in AR saturation-displacement binding parameters. To investigate A₃Rs in CNS, we carried out immunoblot in human brain, resolving two signals, a 52 KDa band with the highest density in hippocampus and a 48 KDa one, slightly more expressed in cortex. Subsequently, A₃R binding was performed by [¹²⁵I]-4-aminobenzyl-5′-N-methylcarboxamidoadenosine ([¹²⁵I]-AB-MECA) in human hippocampus, revealing an high affinity population of sites and another non saturable component. [¹²⁵I]-AB-MECA first site displacement by N⁶ (3-iodobenzyl)adenosine-5′-N-methyluronamide (IB-MECA) and 1,3-dipropyl-8-cyclopenthyl-xanthine (DPCPX) distinguished two affinity sites, being only in part identified as A₃Rs. Therefore, A₃Rs result clearly expressed by Western blot in human brain, but their full CNS characterization needs further investigation.     

Short-term effects of 3,4-methylen-dioxy-metamphetamine (MDMA) on 5-HT(1A) receptors in the rat hippocampus

The first effects of 3,4-methylen-dioxy-metamphetamine (MDMA, “ecstasy”), on serotonin 1A (5-HT_1A) receptors in rat hippocampus were determined by means of [³H]-8-hydroxy-dipropylamino-tetralin ([³H]-8-OH-DPAT) and 5′guanosine-(γ-[³⁵S]-thio)triphosphate ([³⁵S]-GTPγS) binding as well as inhibition of forskolin (FK)-stimulated adenylyl cyclase (AC) activity. The study was completed by [³⁵S]-GTPγS functional autoradiography experiments carried out in frontal sections of rat brain, including the hippocampal region. Results showed that MDMA was either able to displace [³H]-8-OH-DPAT binding (K_i  500 nM) or to reduce the number of specific sites (B_max) without affecting K_d. The drug also failed to change the [³⁵S]-GTPγS binding or to inhibit AC velocity, underlying its behavior as a non-competitive 5-HT_1A receptor antagonist. Further, MDMA (1 or 100 μM), partially antagonized either [³⁵S]-GTPγS binding stimulation of the agonists 5CT and 8-OH-DPAT or the AC inhibition induced by 5CT and DP-5CT. However, in contrast to binding studies, in AC assays the amphetamine displayed an effect also on EC₅₀, always being less potent than the reference antagonist WAY100,635. In functional autoradiography, MDMA behaved either as a partial 5-HT_1A antagonist in limbic areas or, added alone, as an agonist, increasing the coupling signal presumably through 5-HT release from synapses. Interestingly, the selective 5-HT re-uptake inhibitor (SSRI) fluoxetine had no effect on MDMA [³⁵S]-GTPγS binding activation. This latter finding indicates that the amphetamine can release 5-HT via alternative mechanisms to 5-HT transporter binding, probably via membrane synaptic receptors or vesicular transporters. The release of other transmitters is not excluded. Therefore, our results encourage at extending the study of MDMA biochemical profiles, in the attempt to elucidate those amphetamine-induced pathways with a potential for neurotoxicity or psycho-stimulant activity.