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Levodopa-induced dyskinesia is associated with change in striatal cyclic nucleotides levels and cGMP hydrolyzing phosphodiesterase activity
No full textAmantadine prevents levodopa-induced dyskinesia by decreasing cyclic nucleotide phosphodiesterase activity
No full textPhosphodiesterase-10A changes in basal ganglia circuits in two mouse genetic models of DYT1 Dystonia.
No full textDYT1 Dystonia is a movement disorder, caused by a 3-bp deletion in the torsinA gene, characterized by functional rather than structural abnormalities in basal ganglia. Phosphodiesterase-10A (PDE10A) is a key enzyme in the catabolism of cyclic nucleotides, that has peculiar distribution in the basal ganglia. Interestingly, in DYT1 transgenic mouse model overexpressing either human wild-type (hWT) or mutant torsinA (hMT) we have previously demonstrated changes in PDE10A expression and activity, which are opposite in the entopeduncular neucleus and external globus pallidus. We now intend to verify whether similar PDE10A changes could occur also in the basal ganglia of a DYT1 knock-in mouse model, in which the torsinA deletion is inserted in the endogenous gene (Tor1a+/Δgag).
Immunohistochemical analysis was used for identification of PDE10A positive neurons and processes. Quantitative analysis of PDE10A expression was assessed by immunoblotting. PDE10A-dependent cAMP hydrolyzing activity was evaluated using [3H]-cAMP as substrate and papaverine, a well-known PDE10A-inhibitor, on tissue homogenates.
Our studies demonstrate that PDE10A expression and activity were clearly increased in the globus pallidus of hMT and of Tor1a+/Δgag mice compared to controls. In the entopeduncular nucleus, PDE10A expression and activity were significantly decreased both in hWT and hMT mice, and basically reduced in Tor1a+/Δgag mice respect to wild type.
Our findings show a differential expression of PDE10A in the direct and indirect pathway in both DYT1 models. We hypothesize that the 3bp deletion of torsinA may affect expression and/or axonal transport of PDE10A. ΔE-TorsinA could interfere with PDE10A trafficking with mechanisms that are still to be clarified
Opposite changes of Phosphodiesterase-10A in striato-pallidal and striato-entopeduncular pathways of TorsinA DYT1 transgenic mice
No full textPDE10A is up-regulated in Enkephalin striatal projection neurons of a transgenic mouse model of DYT1 Dystonia
No full textIntroduction - Phosphodiesterase-10A (PDE10A), a key enzyme in the catabolism of cAMP in the striatum, is increased in some striatal neurons but decreased in others, throughout the dorsolateral striatum in a transgenic mouse model of DYT1 Dystonia (hMT). We hypothesized that PDE10A either increases or decreases selectively in specific populations of striatal neurons of hMT mice. We undertook a double labelling immunohistochemical study of PDE10A and enkephalin (Enk)-containing neurons, which project to the lateral segment of GP giving rise to the “indirect” pathway.
Methods - Free floating sections of the striatum were incubated with a PDE10A mouse monoclonal antibody, and with rabbit anti-Leucine-Enk and rabbit anti Met-Enk. Sections were subsequently incubated with goat anti rabbit cyanine CyTM2- and goat anti mouse cyanine CyTM3-conjugated secondary antibody.
Results - In control mice, PDE10A immunofluorescence was observed in the vast majority of the striatal neurons with similar intensity in the cell bodies and in the neuropil. Moreover, some cell bodies were expressing a faint ENK immunofluorescence throughout the striatum, colocalizing in PDE10A positive neurons. In hMT mice, some striatal neurons were expressing ENK immunofluorescence; moreover, PDE10A immunofluorescence appeared intense in some neurons, but low in other adjacent neurons throughout the striatum. The subpopulation of striatal neurons expressing up-regulation of PDE10A in hMT mice showed complete overlap with cell bodies expressing ENK immunofluorescences. Conversely, the neurons labelled with low PDE10A immunoreactivity were completely devoid of the ENK immunoreactivity.
Conclusions - Our data demonstrate opposite changes of PDE10A expression in ENK positive and ENK negative striatal neurons of hMT mice. We can speculate that such PDE10A changes in the striatum can map widespread functional impairment of striatal projections, differentially affecting the direct and indirect pathway in basal ganglia circuits of hMT mice
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Different mouse genetic models of human DYT1 dystonia share changes of phosphodiesterase-10A in basal ganglia circuits.
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