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Imbalance of serotonin homeostasis during adulthood affects serotonergic neuronal circuitry
No full textSerotonin (5-hydroxytryptamnine, 5-HT) is a monoaminergic neurotransmitter orchestrating a broad array of cognitive and behavioral processes in the adult brain. The early expression of its receptors during development and the requirement of maternal and placental sources of serotonin to the foetus have led to the hypothesis that 5-HT could act as growth regulator in the fine-tuning of specific morphogenetic events during neurodevelopment. Outcomes from genetic mouse models in which brain 5-HT homeostasis has been perturbed by targeting genes necessary for serotonin reuptake, metabolism or synthesis such as SERT, MAO-A and Tph2, respectively, support this hypothesis. However, evidence of a role for 5-HT in adulthood as a growth regulator or its requirement for maintenance of the proper neuronal circuitry, which is known to be susceptible to 5-HT imbalance during early postnatal stages, is still missing. To bridge this gap we used the Tph2 conditional knock-out (cKO) allele that allows an efficient abrogation of 5-HT synthesis in the adult brain, in combination with the Tph2::GFP allele, in which GFP reporter expression highlights 5-HT neuron fibers and somata. Beside previously reported data showing that the lack of brain serotonin in Tph2 knock-out (KO) mice deeply affects serotonergic circuitry development with a brain region-specific effect, the abrogation of 5-HT synthesis during adulthood produces alterations of serotonergic innervation in rostral brain targets matching those observed in mice with a life-long depletion of brain serotonin. Remarkably, we reported that restoring brain 5-HT signaling in both Tph2 KO and cKO mice by chronic administration of the serotonin precursor 5-hydroxytryptophan (5-HTP) results in a significant reduction in the extent of serotonergic fiber innervation defects, thus demonstrating an unexpectedly high degree of plasticity of the adult serotonergic system in response to changes of 5-HT homeostasis. Moreover, 3D computer-based analysis of serotonergic axon terminal morphology showed that imbalances in brain 5-HT content exert their growth regulatory activity on 5-HT axon terminals by promoting sprouting. Altogether these data demonstrate that a correct 5-HT homeostasis is life-long required to maintain the proper serotonergic innervation of specific rostral brain regions
SEROTONIN DEPLETION AFFECTS DEVELOPMENT AND MAINTENANCE OF SEROTONERGIC NEURONAL CIRCUITS
No full textSerotonin is a neurotransmitter implicated in the modulation
of several behavioral and physiological processes within the central
nervous system (CNS) including mood, control of sleep,
appetite, aggressivity and sexual behavior. In neurons serotonin
is synthesized in two main steps with tryptophan hydroxylase 2
(Tph2) as the rate-limiting enzyme. Serotonergic neurons are
one of the most early born neuronal systems in the mammalian
brain and provide a widespread innervation to the whole CNS.
The synthesis of serotonin during embryonic development
together with a dynamic expression of serotonergic receptors in
the CNS has led to the hypothesis that serotonin could act as a
growth regulator in specific neurodevelopmental events such as
neurogenesis, neuronal migration and circuitry formation.
Although recent discoveries from animal models and human
genetic studies have highlighted the importance of serotonin
homeostasis maintenance during CNS development, the precise
role of this molecule in specific morphogenetic activities
remains poorly understood. To address the consequences of
time-controlled serotonin depletion on CNS development, we
have generated a Tph2 conditional (floxed) allele and used it in
combination with a Tph2-GFP knockin mouse line allowing the
visualization of serotonergic neurons and fibers1. We were able
to demonstrate that abrogation of serotonin synthesis in adult
mice affects the proper serotonergic wiring, thus indicating that
the serotonergic system exhibits a previously unexpected plasticity
in response to serotonin signaling. Our results together with
previous observations suggest that appropriate serotonin homeostasis
is crucial not only for proper development of the serotonergic
neuronal circuit but also for its maintenance during adulthood
Serotonin depletion affects serotonergic neuronal circuits in adult mice
No full textSerotonin is a neurotransmitter synthesized in two steps with tryptophan hydroxylase 2 (Tph2) as the rate-limiting enzyme and it is implicated in the modulation of numerous physiological processes including mood, sleep, aggressivity and sexual behavior. Serotonergic neurons provide a profuse innervation to the whole CNS. The synthesis of serotonin and the expression of its receptors early in embryonic development, as well as its maternal and placental sources to the foetus, have led to the hypothesis that serotonin could act as a growth regulator in specific developmental events such as neurogenesis, neuronal migration and circuitry formation. However, the precise role of serotonin in specific morphogenetic activities during CNS development remains poorly understood. To address the consequences of time-controlled serotonin depletion on CNS development, we have generated a Tph2 conditional (floxed) allele and used it in combination with a Tph2-GFP knockin mouse line allowing the visualization of serotonergic neurons and fibers (Migliarini et al., 2013). Besides the severe abnormalities in the serotonergic circuitry formation observed in Tph2 knockout mice, serotonin depletion in adult animals induces an increase of the density of serotonergic fibers projecting to the hippocampus. These results show that the mature serotonergic system exhibits a previously unexpected plasticity and that appropriate serotonin homeostasis is crucial not only for proper development of the serotonergic neuronal circuit but also for its maintenance during adulthood. Migliarini et al. Mol Psychiatry 2013 18: 1106-18
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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