1,720,954 research outputs found
Statin-induced deficits in memory and learning: A behavioural and electrophysiological investigation
No full textStatins play a crucial role in reducing the risk of death from cardiovascular disease in millions of people worldwide. Recently, data show people taking statins are at increased risk of a number of psychiatric adverse events such as amnesia, anxiety and even aggression. However, there are conflicting epidemiological data and a scarcity of direct experimental evidence that statins can alter neural functioning.
This thesis aimed to investigate the effect of statin treatment on memory in an animal model of spatial memory and learning; the Morris Water maze (MWM) using guinea pigs. The behavioural results demonstrate that statins, independent of their musculoskeletal or liver adverse effects, significantly induced deficits in specific aspects of the MWM. Statins at a clinically equivalent dose of 20mg/d did not affect reference memory directly by affecting latency or distance to platform, but resulted in increased thigmotactic activity. Further behavioural investigations using a higher dose and modified protocol showed once again that statins did not affect spatial reference memory; however, statin treatment for six weeks induced deficits in spatial working memory (short-term memory).
Mechanisms of memory have been hypothesised to result from changes in synaptic plasticity in the hippocampus. Extracellular field recordings of synaptic transmission in area CA1 of hippocampal slices were conducted to assess the effects of statin application on LTP. Statins significantly reduced the amount of LTP expressed in a dose-dependent manner. Further investigations with methyl-beta-cyclodextrin (MBCD), a compound that sequesters cholesterol from lipid membranes, demonstrated that statins act independently of cholesterol reduction to decrease the expression of LTP. Furthermore, statins did not affect paired pulse facilitation, but induction of LTP reduced the paired pulse ratio (PPR) in statin-treated slices. These results therefore suggest that statins may induce paired pulse depression after the induction of LTP.
To assess these findings further and provide clinical consensus, the effect of six weeks of chronic statin administration on LTP was investigated. Hippocampal slices from statin-treated animals showed reduced expression of LTP compared with vehicle treated animals; however, this was not statistically significant. It is possible that behavioural training prior to electrophysiological assessment could have obscured from detection of any deficits in LTP following chronic statin treatment. To further investigate the molecular mechanisms of statin-induced deficits, western blot analysis of GluN1 and GluA1, specific subunits of glutamatergic receptors known to be critically involved in memory and learning were assessed. Statins induced a 1.5 fold increase in GluA1 but did not affect the expression of GluN1.
In conclusion, the results of this thesis demonstrate that statins administered to healthy guinea pigs, at clinically relevant doses, can induce specific behavioural deficits in spatial memory. Furthermore, statins attenuated hippocampal LTP (in vitro), independently of their cholesterol-lowering properties. This thesis has taken the first step in providing evidence to suggest how statins may induce deficits in memory and learning, and in the process has led to new understandings of the role of statins in hippocampal synaptic plasticity, memory and learning
Statin-induced deficits in memory and learning: A behavioural and electrophysiological investigation
No full textStatins play a crucial role in reducing the risk of death from cardiovascular disease in millions of people worldwide. Recently, data show people taking statins are at increased risk of a number of psychiatric adverse events such as amnesia, anxiety and even aggression. However, there are conflicting epidemiological data and a scarcity of direct experimental evidence that statins can alter neural functioning.
This thesis aimed to investigate the effect of statin treatment on memory in an animal model of spatial memory and learning; the Morris Water maze (MWM) using guinea pigs. The behavioural results demonstrate that statins, independent of their musculoskeletal or liver adverse effects, significantly induced deficits in specific aspects of the MWM. Statins at a clinically equivalent dose of 20mg/d did not affect reference memory directly by affecting latency or distance to platform, but resulted in increased thigmotactic activity. Further behavioural investigations using a higher dose and modified protocol showed once again that statins did not affect spatial reference memory; however, statin treatment for six weeks induced deficits in spatial working memory (short-term memory).
Mechanisms of memory have been hypothesised to result from changes in synaptic plasticity in the hippocampus. Extracellular field recordings of synaptic transmission in area CA1 of hippocampal slices were conducted to assess the effects of statin application on LTP. Statins significantly reduced the amount of LTP expressed in a dose-dependent manner. Further investigations with methyl-beta-cyclodextrin (MBCD), a compound that sequesters cholesterol from lipid membranes, demonstrated that statins act independently of cholesterol reduction to decrease the expression of LTP. Furthermore, statins did not affect paired pulse facilitation, but induction of LTP reduced the paired pulse ratio (PPR) in statin-treated slices. These results therefore suggest that statins may induce paired pulse depression after the induction of LTP.
To assess these findings further and provide clinical consensus, the effect of six weeks of chronic statin administration on LTP was investigated. Hippocampal slices from statin-treated animals showed reduced expression of LTP compared with vehicle treated animals; however, this was not statistically significant. It is possible that behavioural training prior to electrophysiological assessment could have obscured from detection of any deficits in LTP following chronic statin treatment. To further investigate the molecular mechanisms of statin-induced deficits, western blot analysis of GluN1 and GluA1, specific subunits of glutamatergic receptors known to be critically involved in memory and learning were assessed. Statins induced a 1.5 fold increase in GluA1 but did not affect the expression of GluN1.
In conclusion, the results of this thesis demonstrate that statins administered to healthy guinea pigs, at clinically relevant doses, can induce specific behavioural deficits in spatial memory. Furthermore, statins attenuated hippocampal LTP (in vitro), independently of their cholesterol-lowering properties. This thesis has taken the first step in providing evidence to suggest how statins may induce deficits in memory and learning, and in the process has led to new understandings of the role of statins in hippocampal synaptic plasticity, memory and learning
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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