The ability of D 9 -THCV to reduce motor inhibition and provide neuroprotection was investigated in rats lesioned with 6-hydroxydopamine and in mice lesioned with lipopolysaccharide (LPS). KEY RESULTS Acute administration of D 9-THCV attenuated the motor inhibition caused by 6-hydroxydopamine, presumably through changes in glutamatergic transmission. Moreover, chronic administration of D 9 -THCV attenuated the loss of tyrosine hydroxylase-positive neurones caused by 6-hydroxydopamine in the substantia nigra, through an effect related to its antioxidant properties (it was reproduced by cannabidiol -enriched botanical extract). In addition, CB2 receptor-deficient mice responded to 6-hydroxydopamine in a similar manner to wild-type animals, and CB2 receptors were poorly up-regulated in the rat substantia nigra in response to 6-hydroxydopamine. By contrast, the substantia nigra of mice that had been injected with LPS exhibited a greater up-regulation of CB2 receptors. In these animals, D 9-THCV also caused preservation of tyrosine hydroxylase-positive neurones. This effect probably involved CB2 receptors as it was also elicited by the selective CB2 receptor agonist, HU-308, and CB2 receptor-deficient mice were more vulnerable to LPS lesions. CONCLUSIONS AND IMPLICATIONSGiven its antioxidant properties and its ability to activate CB2 but to block CB1 receptors, D 9-THCV has a promising pharmacological profile for delaying disease progression in PD and also for ameliorating parkinsonian symptoms.

Recent evidence obtained in rat models of Parkinson's disease showed that the density of cannabinoid CB1 receptors and their endogenous ligands increase in basal ganglia. However, no data exists from post-mortem brain of humans affected by Parkinson's disease or from primate models of the disorder. In the present study, we examined CB1 receptor binding and the magnitude of the stimulation by WIN55,212-2, a specific CB1 receptor agonist, of [35S]GTPgammaS binding to membrane fractions from the basal ganglia of patients affected by Parkinson's disease. In Parkinson's disease, WIN55,212-2-stimulated [35S]GTPgammaS binding in the caudate nucleus, putamen, lateral globus pallidus and substantia nigra was increased, thus indicating a more effective activation of GTP-binding protein-coupled signalling mechanisms via CB1 receptors. This was accompanied by an increase in CB1 receptor binding in the caudate nucleus and the putamen, although no changes were observed in the lateral globus pallidus and the substantia nigra. Because Parkinson's disease patients had been chronically treated with l-DOPA, brains were studied from normal common marmosets and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated animals with and without chronic L-DOPA treatment. MPTP-lesioned marmosets had increased CB1 receptor binding in the caudate nucleus and the putamen compared to control marmosets, as well as increased stimulation of [35S]GTPgammaS binding by WIN55,212-2. However, following l-DOPA treatment these parameters returned towards control values. The results indicate that a nigro-striatal lesion is associated with an increase in CB1 receptors in the basal ganglia in humans and nonhuman primates and that this increase could be reversed by chronic l-DOPA therapy. The data suggest that CB1 receptor blockade might be useful as an adjuvant for the treatment of parkinsonian motor symptoms.

Cannabinoid CB(1) receptors emerge early in the rat brain during prenatal development, supporting their potential participation in events related to neural development. In the present investigation, we completed earlier studies, analyzing CB(1) receptor binding and mRNA expression by using autoradiography and in situ hybridization, respectively, in the brain of rat fetuses at gestational day (GD) 21 and of newborns at postnatal days (PND) 1 and 5, in comparison with the adult brain. These analyses were paralleled by quantitation of levels of anandamide and its precursor, N-arachidonoyl-phosphatidylethanolamine (NAPE), and of 2-arachidonoyl-glycerol (2-AG), carried out by using gas chromatography / mass spectrometry of the tri-methyl-sylyl-ether derivatives. As expected, CB(1) receptor binding was detected at GD21 in a variety of brain structures. In most of them, such as the hippocampus, cerebral cortex, cerebellum, basal ganglia, and limbic nuclei, there were no marked differences in the density of CB(1) receptors in animals at GD21 as compared to early newborns (PND1 and 5), although it markedly increased in these regions in adulthood. However, with the exception of the cerebellum and, in part, the caudate-putamen, the pattern observed for binding in these regions was clearly different from that observed for mRNA expression of the CB(1) receptor, which currently exhibited the highest levels at PND1 and the lowest in the adult brain. This was also seen in the basolateral amygdaloid nucleus, ventromedial hypothalamic nucleus, medial habenula, and other structures. In the caudate-putamen and, particularly, in the cerebellum, mRNA expression was higher in the adult brain as compared with other ages. As previously reported, specific binding for CB(1) receptors was also detected at GD21 in white matter areas, such as the corpus callosum, anterior commissure, fornix, fimbria, stria medullaris, stria terminalis, and fasciculus retroflexum. With the exception of the anterior commissure and the fimbria, specific binding progressively decreased at PND1 and PND5 until disappearing in the adult brain. In the fimbria, the highest values of binding were seen at PND1, but binding also completely disappeared in the adult brain, whereas in the anterior commissure, specific binding at PND1 and PND5 was lesser than that observed at GD21 and, particularly, in adulthood. CB(1) receptor mRNA expression was not detected in these white matter areas, thus dismissing the possible presence of these receptors in glial cells rather than in neuronal axons. However, mRNA expression was detected in the brainstem, an area also rich in white matter, and it mostly correlated with receptor binding, exhibiting a progressive decrease from GD21 up to adulthood. CB(1) receptor mRNA expression was also detected at GD21 in atypical areas where binding was not detected. These areas are proliferative regions, such as the subventricular zones of the neocortex, striatum, and nucleus accumbens. This atypical location only persisted at PND1 and PND5 in the st...

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Summary Birds are important in the ecology of Borrelia burgdorferi sensu lato (s.l.) because they are important hosts for vector tick immature stages and are known reservoirs for some Borrelia genospecies. The aim of our study was to assess the role of common passerine bird species as reservoirs for B. burgdorferi s.l. in Western Europe. We surveyed birds in enzootic areas in Portugal, where no information is available for birds as reservoirs for this aetiologic agent and where B. lusitaniae, for which few reservoirs have been identified, is the dominant genospecies. Twenty‐three birds (2.9%), including Turdus merula, T. philomelos, Parus major and Fringilla coelebs harboured infected ticks, but only Turdus sp. harboured infected tick larvae. In one study area, although B. lusitaniae was dominant in questing Ixodes ricinus, no ticks feeding on birds were infected with this genospecies, and B. valaisiana was the dominant genospecies in I. ricinus larvae feeding on birds. In the other area ticks collected from birds were mainly I. frontalis which were infected with B. turdi. Two skin biopsies (4.2%) from two T. merula were positive, one for B. valaisiana and the other for B. turdi. This is the first report for B. turdi in Western Europe.

Seed dispersal is a central process in plant ecology with consequences for species composition and habitat structure. Some bird species are known to disperse the seeds they ingest, whereas others, termed 'seed predators', digest them and apparently play no part in dispersal, but it is not clear if these are discrete strategies or simply the ends of a continuum. We assessed dispersal effectiveness by combining analysis of faecal samples and bird density. The droppings of seed dispersers contained more entire seeds than those of typical seed predators, but over a quarter of the droppings of seed predators contained whole seeds. This effect was further magnified when bird density was taken into account, and was driven largely by one frequent interaction: the Chaffinch Fringilla coelebs, a typical seed predator and the most abundant bird species in the area and dispersed seeds of Leycesteria formosa, a non-native plant with berry-like fruits. These results suggest the existence of a continuum between seed predators and seed dispersers.

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