Where are the Caribs? Ancient DNA from ceramic period human remains in the Lesser Antilles.

The identity and history of the indigenous groups who occupied the Lesser Antilles during the ceramic periods remain highly controversial. Although recent archaeological evidence has challenged hypotheses concerning the organization of human groups in this region, more biological data are needed to fully inform the discussion. Our study provides, to our knowledge, the first palaeogenetic data for Late Ceramic groups of the Guadeloupe archipelago, yielding crucial information concerning the identities of these groups. Despite the generally poor DNA preservation in the tested remains, we were able to retrieve Hypervariable Region 1 sequences from 11 individuals and mitochondrial single-nucleotide polymorphisms from 13 individuals. These novel data provide interesting preliminary results in favour of a common origin for all Saladoid Caribbean communities, i.e. the first ceramic groups of the region, as well as for a local continuity between the Saladoid and post-Saladoid groups. A combination of the genetic data obtained and several pieces of cultural evidence allows us to propose that two different groups inhabited the Guadeloupe archipelago during the Late Ceramic period, with the possible occupation of the La Désirade and Marie-Galante islands by groups affiliated with the Taíno communities. The working hypotheses proposed here appear consistent with recent archaeological evidence.

5-HT1B receptor binding in degenerative movement disorders.

Using [3H]sumatriptan as a radioligand, 5-hydroxytryptamine (5-HT)1B receptors were examined in posterior striatum and midbrain post-mortem tissue sections of 12 patients who had died from representative degenerative movement disorders as compared to nine controls. In the control human basal ganglia, the highest densities of [3H]sumatriptan binding were observed in the globus pallidus and substantia nigra. No significant change in the density of [3H]sumatriptan binding sites was found in the striatum and substantia nigra of the six Parkinson's disease brains. In the two brains from patients with progressive supranuclear palsy an increase was found in the densities of [3H]sumatriptan binding sites, most marked in the substantia nigra. In contrast, [3H]sumatriptan labelling was almost absent in the striatonigral degeneration brain and was markedly reduced in the three Huntington's disease brains. This study indicates that the status of 5-HT1B receptors is different in each degenerative movement disorder and suggests that human 5-HT1B receptors are located somatodendritically on GABAergic and peptidergic caudate-putamen neurons which project to the substantia nigra and globus pallidus, where these receptors are presynaptic.

Differential distribution of [3H]sumatriptan binding sites (5-HT1B, 5-HT1D and 5-HT1F receptors) in human brain: focus on brainstem and spinal cord.

We report on the autoradiographic distribution of 5-HT1B, 5-HT1D and 5-HT1F receptor subtypes in human brain, focusing on the brainstem and cervical spinal cord. We have used [3H]sumatriptan as a radioligand in the presence of suitable concentrations of 5-CT (5-carboxamidotryptamine) to define 5-HT1F receptors, and ketanserin, to discriminate between 5-HT1B and 5-HT1D receptors. In the brainstem the highest concentrations of [3H]sumatriptan binding sites were seen in substantia nigra. The spinal trigeminal nucleus, substantia gelatinosa of the spinal cord, nucleus of the tractus solitarius and periaqueductal grey, also showed significant levels of [3H]sumatriptan binding sites. In the brainstem and spinal cord the total population of 5-CT-insensitive receptors, corresponding to 5-HT1F receptors, ranged from 9.8% in the periaqueductal grey to 53.4% in the substantia gelatinosa. This population represented 67.0% of binding in layer V of the frontal cortex. The decrease in [3H]sumatriptan binding in the presence of 200 nM ketanserin, indicative of the presence of 5-HT1D receptors, was very limited throughout the human brain, only reaching 20% of total specific binding over the periaqueductal grey. The proportion of [3H]sumatriptan binding sites displaced by 5-CT and insensitive to ketanserin, corresponding to 5-HT1B receptors, was, in general, the most abundant, ranging from 43.8% in substantia gelatinosa to 69.9% in the periaqueductal grey. Significant levels of 5-HT1B and 5-HT1D receptors found in migraine control pain areas suggest their involvement in antinociceptive mechanisms.

Identification and characterization of a new serotonergic recognition site with high affinity for 5-carboxamidotryptamine in mammalian brain.

We analyzed the existence of an additional serotonin (5-HT) receptor subtype, sensitive to 5-carboxamidotryptamine, in the mammalian brain. Radioligand binding studies with [3H]5-HT were carried out in rat, guinea pig, and human brain membranes, in the presence of unlabeled drugs to mask the binding to all known 5-HT receptors, with the exception of 5-HT1E sites. Under these conditions, unlabeled 5-carboxamidotryptamine still showed a biphasic competition curve with a nanomolar affinity component. Saturation studies with 5-[3H]carboxamidotryptamine were carried out in the presence of (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin, mesulergine, and ergotamine, to mask the binding to all receptors known to be labeled by 5-carboxamidotryptamine. These studies showed the existence in cortex and hippocampus from guinea pig and human brain of a remaining binding site with high affinity (pK(D) = 7.8-8.1) and a unique pharmacological profile. 5-HT and 5-carboxamidotryptamine showed nanomolar affinity, whereas 5-methoxytryptamine recognized this binding site with intermediate affinity. Other drugs exhibited low or very low potency in inhibiting this binding. The addition of 5'-guanylylimidodiphosphate significantly reduced the number of binding sites labeled by 5-[3H]carboxamidotryptamine, in the presence of the masking drugs described above, indicating the interaction with a GTP-binding protein. Preliminary autoradiographic studies in human brain appear to indicate that this 5-HT binding site is present in areas such as the globus pallidus, neocortex, and hippocampus, among others.

Autoradiographic distribution of [3H]sumatriptan-binding sites in post-mortem human brain.

The anatomical distribution of [3H]sumatriptan-binding sites was analysed in brain tissue sections from 11 subjects. Relevant concentrations of [3H]sumatriptan-binding sites were seen in areas such as visual cortex > locus niger > globus pallidus > layers IV-V of the frontal cortex > subiculum > entorhinal cortex > nucleus tractus solitarius > nucleus trigeminalis caudalis. This distribution of [3H]sumatriptan-binding sites in the human brain shows some differences when compared with that of 5HT1D receptors, confirming that, besides 5HT1D, sumatriptan also binds to 5HT1F receptor subtype. Some species differences are evident between the distribution of [3H]sumatriptan-binding sites in the human brain and that reported for guinea-pig and rat brains, emphasizing that caution is needed in extrapolating experimental data from animals to humans. Furthermore, these data help to explain some of the therapeutic actions of sumatriptan. The remarkable levels of binding found in areas as nucleus tractus solitarius and nucleus trigeminalis caudalis suggest that in migraine attacks sumatriptan could exert its specific anti-emetic effects and, partly at least, induce analgesia by directly acting over these brain nuclei.

[3H]Sumatriptan binding sites in human brain: regional-dependent labelling of 5-HT1D and 5-HT1F receptors.

The general properties of [3H]sumatriptan binding sites in postmortem human brain tissue sections are described. High concentrations of autoradiographic grains were seen in globus pallidus = substantia nigra > cortex > putamen > hippocampus. While 5-HT (5-hydroxytryptamine) displaced in all regions more than 90% of [3H]sumatriptan binding, the level of binding inhibited by 5-CT (5-carboxamidotryptamine) varied in each region. Although the binding inhibited by 5-CT in some regions such as globus pallidus and substantia nigra was equivalent to that obtained with 5-HT, in cortical areas, such as frontal cortex and hippocampus, a substantial level of binding insensitive to 5-CT was seen. In addition, in membrane binding assays, 10 nM metergoline displaced most [3H]sumatriptan specific binding in striatum and only 16% in frontal cortex. In the human brain sumatriptan binds to at least two 5-HT1 receptors, 5-HT1D and 5-HT1F.