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Prenatal valproate in rodents as a tool to understand the neural underpinnings of social dysfunctions in autism spectrum disorder
No full textImpairments in social interaction and verbal and non verbal communication are among the main features of Autism Spectrum Disorder (ASD). The causes of ASD are still unknown but the research efforts of the last decade have identified a number of factors (rare gene mutations, gene variations and adverse environmental events) that, interacting in complex ways, affect early brain development. The clinical evidence that prenatal exposure to the antiepileptic drug valproate (VPA) is associated with increased risk of neurodevelopmental delay, cognitive deficits and autism in children, has drawn the attention of scientists on VPA as a tool to unravel the environment contribution to ASD risk in children. In agreement with the clinical evidence, rodents prenatally exposed to VPA display behavioral anomalies resembling ASD symptoms. The mechanisms by which administration of VPA in pregnancy increases the risk of autism are still far to be clear as are still undetermined the specific targets of VPA in the developing brain both in humans and rodents. However, the robustness of the behavioral alterations, mainly in the social domain, and the neural/molecular changes revealed so far support the VPA model as a reliable instrument to investigate the neural underpinnings of social impairment. Here we provide an update of preclinical studies on prenatal exposure to VPA in rodents with a focus on the social and communication deficits induced by VPA, discussing potential pitfalls and future directions in this research field and corroborating the potential of the VPA model to identify new pharmacological targets for ASD
In vivo co-exposure monitoring to Pb and Mn from conception until adulthood
No full textOne of the most important concerns for public health related to toxic elements is exposure to Lead (Pb). By now there is no evidence that Pb has any benefit or an essential role for humans. On the contrary, several studies have demonstrated that there is no safe threshold of exposure, especially for children. On the other hand, Manganese (Mn) is an essential element for humans. It works as a cofactor for a variety of enzymes, therefore, is a crucial nutrient.
Our experiment was organized to increase the understanding, by exposure of mice in vivo, of the behavior for co-exposure to Pb and Mn. Shortly, four groups of mother were divided into: control, Pb exposure, Mn exposure, and Pb + Mn exposure groups respectively. The exposure via was done through drinking water and Pb solution had a 100 ppm concentration and Mn solution had 2 g/L concentration. Exposure begins 5 weeks before the delivery.
Then the offspring were grouped according to the mother exposure group, and the sub-grouped until they reach the ages of 0 –3 (0-3 PND), 14 –18 (18 PND), and 60 (60 PND) post-natal days respectively.
During this period the groups 18 PND and 60 PND continue the exposure via lactation. The exposure continues, until the sacrifice, for the through lactation until the 21 days after born. When every group reach the need its age, they were sacrificed and the blood samples, among others, were taken for analyse the element concentrations.
The metal concentration analysis for the blood samples was performed using ICP-MS. Briefly, the samples were digested using ultrapure HNO3 at 80 °C, from it the analytical solution was prepared. As quality control were used CCL® and SERONORM® Level 1 and 2. The full procedure is reported elsewhere.
The principal statistic for the concentrations are presented in the Tables 1 and 2.
Table 1. Pb concentrations in ppb (μg/L)
Offspring ́s age Exposure group
1 Control 2 Pb exposure 3 Mn exposure 4 Pb + Mn coex
n x̄ sd n x̄ sd n x̄ sd n x̄ sd
0-3 PND 11 2.68 2.11 7 280.81 149.15 17 2.86 4.14 30 178.98 69.55
18 PND 18 2.80 1.41 17 341.16 107.99 17 3.49 1.04 54 249.88 71.00
60 PND 18 1.56 2.35 18 9.33 3.09 20 1.12 0.58 42 3.70 2.05
Table 2. Mn concentrations in ppb (μg/L)
Offspring ́s age Exposure group
1 Control 2 Pb exposure 3 Mn exposure 4 Pb + Mn coex
n x̄ sd n x̄ sd n x̄ sd n x̄ sd
0-3 PND 11 37.10 55.36 7 80.26 136.19 17 134.61 119.28 30 262.66 429.80
18 PND 18 11.77 2.05 17 15.57 5.24 17 63.52 33.52 54 87.07 43.31
60 PND 18 11.42 3.65 18 9.33 3.09 20 10.85 3.92 42 10.1 3.24
Here the control groups were expected to show the lower concentration, base line, for each mice age group. The lower values for Pb and Mn correspond to the age PND (60) with an average of 1.56 ± 2.35 ppb and 11.42 ± 3.65 ppb for Pb and Mn respectably. On the other hand, the higher values for Pb correspond to “Pb exposure” group at the age of 18 PND. This due probably to the constant exposure of the subjects from the maternal womb until the end of their life. The value found for Pb corresponds to 341.16 ± 107.16 ppb. Nevertheless, for the Mn concentrations, the higher values were presented for the “Pb + Mn coex” at the age of 0-3 PND, with an average value of 262.66 ± 429.80 ppb.
A comparison between the values got to Pb “Pb exposure” and “Pb + Mn coex” show that the presence of Mn have inhibitory effect in the absorption of Pb for the subject. Meanwhile the behavior for the Mn seems to work at contrary. When the groups “Mn + exposure” and “Pb + M coex” are compared the amount of Mn seems to increase when Pb is present. This can reveal a tide relationship between the metabolism involving these metals.
Due to the exposure (single and co-exposure) is finished 20 days after the delivery, the age group of 60 PDN, seems to return to base values equal as the control group. In this way is possible to hypothesize that for exposure time of 20 days, a period of 40 days is enough to eliminated from the blood the excess of Pb and Mn. For a better understanding of the metabolism pathways of the storage organs, a set of samples from liver, bones, and brain were collected from the subjects and will be analysed to continue the study
Neonatal exposure to chlorpyrifos affects maternal responses and maternal aggression of female mice in adulthood
No full textCD-1 mice were exposed to the organophosphate pesticide chlorpyrifos (CPF) throughout postnatal days (PND) 11-14 at the subtoxic dose of 3 mg/kg. At adolescent age, females and males underwent a sociability test in which level of sociability and social preference were measured. At adulthood only females' behavior was analyzed. Maternal behavior of CPF-exposed females was assessed on postpartum day 1 after removal of the pups for 1 h, while anxiety levels were measured in a 5 min dark-light test on postpartum day 2. Nest defense response to an unfamiliar male intruder was assessed on postpartum day 7. In addition, from birth to postpartum day 7 a detailed analysis of nest building activity was carried out. Neonatal CPF exposure does not interfere with social behavior and social preferences at adolescence, whereas at adulthood it induces significant behavioral alterations in lactating females. Motivation to build and defend the nest was decreased in CPF females that were also less anxious than controls in the dark-light paradigm. These results confirm that developmental exposure to CPF induces long-lasting alterations in selected sexual-dimorphic responses of the adult social repertoire, and suggest that early exposure to CPF might interfere with hypothalamic neuroendocrine mechanisms regulating social responses. © 2008 Elsevier Inc. All rights reserved
Developmental exposure to Pb and Mn in mice: Longitudinal studies
No full textDevelopmental exposure to metals may have serious consequences for mental health1,2. Longitudinal in vivo studies can improve our ability to identify mechanisms of metal neurotoxicity and consistency of long term effects. In our first study, we developmentally exposed CD1 outbred mice to Pb, in the second one to a mixture of Pb and Mn. We mimicked the real-life exposure scenario with low, human-related levels of the two metals administered in drinking water to female mice throughout pre-conception, gestation and lactation periods. Behavioural tests were subsequently conducted in the offspring (to evaluate metal effects on neonatal, juvenile and adult behavioural profiles). Metal levels were monitored in blood, brain and bone at different ages.
The first study revealed the effect of Pb on selected neonatal responses (reduced locomotor activity in the nest area during homing test on PND 11 and spatial learning and memory performances at adulthood. These behavioural alterations were observed in animals with blood lead levels (BBLs) below 5 μg/dL, the identified blood Pb reference value for children by the Center for Disease Control and Prevention (CDC)3, thus confirming that that there is no safe level for Pb. Moreover, Pb monitoring in different tissue showed that brain Pb levels remain significantly higher than controls at later ages, when BLLs did not longer differ. Interestingly, adult Pb-exposed males appeared more vulnerable than females to detrimental Pb effects on spatial learning and memory, as previously reported4; brain Pb levels in males did not differ from females, suggesting a different Pb neurodevelopmental effect rather than higher accumulation in male brains.
In the second experiment, whereas most Pb effects of the previous study were confirmed, co-exposure of Pb and Mn did not show synergistic effect of the two metals; Mn-exposed males appeared selectively impaired in reactivity to social/olfactory cues, a result that certainly needs further investigation. As a whole, we found behavioural effects of developmental metal exposures, suggesting that Pb and Mn interfered with maturation of cognitive and social competencies
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
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe 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
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