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Effect of Melanotan-II on brain Fos immunoreactivity and oxytocin neuronal activity and secretion in rats
Get PDFMelanocortins stimulate the central oxytocin systems which are involved in regulating social behaviours. Alterations in central oxytocin have been linked to neurological disorders such as autism, and melanocortins have been proposed for therapeutic treatment. Here, we investigated how systemic administration of melanotan-II (MT-II), a melanocortin agonist, affects oxytocin neuronal activity and secretion in rats. Our results show that intravenous (i.v.), but not intranasal, administration of MT-II markedly induced Fos expression in magnocellular neurones of the supraoptic (SON) and paraventricular nuclei (PVN) of the hypothalamus, and this response was attenuated by prior intracerebroventricular (i.c.v.) administration of the melanocortin antagonist, SHU-9119. Electrophysiological recordings from identified magnocellular neurones of the SON showed that i.v. administration of MT-II increased the firing rate in oxytocin neurones, but did not trigger somatodendritic oxytocin release within the SON as measured by microdialysis. Our data suggest that, after intravenous, but not intranasal, administration of MT-II, the activity of magnocellular neurones of the SON is increased. Since previous studies showed that SON oxytocin neurones are inhibited in response to direct application of melanocortin agonists, the actions of i.v. MT-II are likely to be mediated at least partly indirectly, possibly by activation of inputs from the caudal brainstem, where MT-II also increased Fos expression. This article is protected by copyright. All rights reserved.</p
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
A computational approach to magnocellular oxytocin neuron dynamics
Get PDFMagnocellular oxytocin neurones, found mainly in the supraoptic nucleus and in the
paraventricular nucleus of the hypothalamus, project their axons to the posterior
pituitary, from where they secrete oxytocin into the bloodstream. Oxytocin is well
known for its essential role in breastfeeding and for facilitating labour. However, in
the last decades oxytocin has also been recognised to have roles in energy balance
and osmotic pressure balance.
During breastfeeding and labour, the spiking activity of oxytocin neurones alternates
between long periods of slow basal activity and a few seconds of bursting, when
oxytocin neurones fire synchronously at up to 100 spikes per second. Energy and
osmotic pressure balance are associated with small to medium linear alterations of
the basal activity of oxytocin neurons.
A computational model was developed to simulate the spiking activity of oxytocin
neurones described in the literature. The simulations mimicked their basal activity,
their response to cholecystokinin (CCK), a gut peptide involved in energy balance,
and their spiking response to osmotic pressure. However, the final product of
oxytocin neurones is the secreted oxytocin and its plasma concentration. Thus, it
was developed a secretion model matched to experimental data in the literature,
coupled it with the spiking model, and added a model for oxytocin clearance from
plasma. That allowed simulating the plasma oxytocin response to CCK and to
changes in the osmotic pressure. In addition, the model offered important insights. It
supports the necessity of a depolarization after potential (DAP) in some oxytocin
neuron membranes, the essential role of inhibitory inputs during the oxytocin
osmotic response, a new mechanism for partially explaining oxytocin response to
hypovolemia, and explains the role of the after hyperpolarizing (AHP) current as a
filter of synaptic inputs to oxytocin neurones
Influence of early life and positive affect on feeding behaviour and food choice in the rat
Get PDFIn recent years, worldwide obesity rates have risen dramatically, putting major strain on
public health systems and the economy. Obesity is a multifaceted disease and its
development can be influenced by a variety of factors including genetic, psychological and
environmental influences. One area of current focus in obesity research is that of early life
programming. It has been well-established that certain early life factors can impact the
physiology and behaviour of the offspring. Because of this, early life programming has
become increasingly well studied in order to develop a deeper understanding of how early
life can influence obesity development. Another area of interest lies in positive mood.
While there has been much research into the effects of negative states such as stress and
anxiety on feeding behaviour, there is still very little known about how positive states can
influence food choice. Using rat models of prenatal stress, neonatal overnutrition and
positive affect, this thesis aimed to investigate the effects of early life and mood factors on
feeding behaviour and food choice.
Prenatal stress has been extensively studied and is characterised by an enhanced stress
response in the offspring. Using two rat models of prenatal stress- social and restraint
stress, the effects of prenatal stress on feeding behaviour and food choice in the offspring
were examined. In both models, no effects of prenatal stress on either food intake or food
choice were observed. However, in both cases the expected alterations to the offspring’s
stress responses when exposed to an acute stressor were not replicated. This may suggest
that models of prenatal stress are not as robust as often cited in the literature.
As well as the prenatal environment, the early postnatal environment is also able to
influence physiology and behaviour. In terms of obesity, a well-studied model is that of
small litter size. Rats from small litters are over-nourished as neonates and because of this
illustrate an increased body weight that persists throughout life. While this increase in
weight gain has been well-established, there is no evidence examining the impact of
neonatal overnutrition on long-term food choice. Therefore, food intake and food choice
were measured in small and control litter rats over a 10-week period. When placed on an
ad lib diet of bland chow, sucrose and lard, small litter rats consumed significantly more
chow than control litter rats, whilst maintaining similar consumption of lard and sucrose.
However, when offered a high-fat high-sugar (HFHS) pellet for two hours a day alongside ad
lib chow, small litter rats illustrated increased consumption of the HFHS pellet compared to
controls. This suggests that small litter rats may be programmed to adjust their food
choices to enable them to maintain their increased body weight in comparison to controls.
To examine the effects of positive affect on feeding behaviour, ultrasonic vocalisations
(USVs, specifically those at 50 kHz) were used as a measure of positive affect in rats. In
order to examine whether access to a food reward could induce a positive affect (as
measured by an increase in 50 kHz USVs), rats were schedule-fed sweetened condensed
milk and USVs measured before, during and after consumption. No differences in 50 kHz
USVs were observed suggesting that a palatable food, whilst rewarding, does not alter
affective state in the rat. Using heterospecific social contact (a tickling interaction
simulating rough and tumble play) to induce positive affect, rats were presented with an
hour-long sucrose preference test following social contact in order to examine the impact
of positive affect on food choice. While no differences in sucrose consumption were found,
a reduced sucrose preference was observed in rats receiving social contact compared to
controls, suggesting that positive affect may play a role in mediating food choice. Finally,
the effects of fasting (a negative stimulus thought to reduce 50 kHz USVs) and a food
reward on motivation for social contact were examined. Both fasting and access to a food
reward resulted in no differences in conditioned place preference to receive social
interaction.
Overall, the results obtained in this thesis implicate both neonatal overnutrition and, for
the first time, positive affect as possible mediators of food choice, although further studies
are required to fully establish these effects. Importantly, these results also raise questions
regarding the reproducibility of some early life models, such as prenatal stress, and
highlights the importance of sharing precise experimental protocols across laboratories.
Through further investigation of the effects of early life and affective states on food
consumption and choice, and the mechanisms behind these, this may enable the
development of therapeutic interventions and preventative measures that can help slow,
or even reverse, the global obesity epidemic
Behavioural and neural responses to the consumption of palatable, high-sugar food in rats
Get PDFA complex system exists to monitor the body’s energy status and regulate food
intake and energy expenditure to maintain a constant body weight. However, this
homeostatic system is not the sole system regulating appetite. The hedonic system
comprised of the mesolimbic reward pathway influences motivation to eat and acts
alongside the homeostatic system to control feeding behaviours. It is often assumed
that the hedonic system promotes the consumption of palatable, energy-dense
foods and this can disrupt homeostatic mechanisms regulating food intake, resulting
in energy overconsumption and weight gain in the long term. Yet, it is unclear to
what extent the homeostatic system can defend body weight in an environment rich
in palatable, energy-dense foods.
I hypothesised that the homeostatic system compensates for the energy in palatable
foods by reducing subsequent energy consumption, defined as homeostatic caloric
compensation. I investigated homeostatic caloric compensation in a rat model of
restricted palatable, high-sugar food access. Rats were schedule-fed moderate
amounts of sweetened condensed milk (SCM) daily in addition to ad lib bland diet
access. Both male and female rats calorically compensated for the energy
consumed from moderate amounts of SCM through a robust and accurate reduction
in energy consumed from bland diet, resulting in no short-term changes in body
weight gain. However, homeostatic responses were limited as male rats were
unable to fully calorically compensate for the scheduled-feeding of large amounts of
SCM, an apparent loss of homeostatic control. It was not investigated whether
female rats are also unable to fully calorically compensate for large amounts of
SCM. It is possible that male rats consume these large amounts of SCM due to
hedonic drive but continue to eat bland diet to acquire nutrients that are not present
in SCM. To determine whether male rats defend bland diet consumption due to
nutrient requirements, rats were schedule-fed large amounts of SCM enriched with
protein or fibre. However, male rats did not fully calorically compensate for the
energy in large amounts of SCM when enriched with protein or fibre. Overall, these
findings demonstrate that the homeostatic system is able to respond to the hedonic
consumption of palatable food through caloric compensatory mechanisms to defend
body weight. However, it appears that the homeostatic system is unable to
effectively respond to excessive hedonic palatable food consumption through caloric
compensation alone.
To shed light on what homeostatic mechanisms may underlie this compensatory
behaviour, I used expression of the immediate early gene c-Fos to investigate
neuronal activity following the scheduled-feeding of moderate amounts of SCM in
male rats. c-Fos expression was increased in the ventral tegmental area of the
mesolimbic reward pathway and in the lateral hypothalamus. The lateral
hypothalamus has been proposed to act as an interface between homeostatic and
hedonic systems. Therefore, in response to the hedonic consumption of palatable
food, the homeostatic system and reward pathway may interact. Additionally, c-Fos
expression was increased in satiety mediating brain regions of the homeostatic
system, including the nucleus of the solitary tract and dorsomedial hypothalamus.
This suggests that the homeostatic system may compensate for the energy in the
palatable food by reducing subsequent food intake through inducing satiety.
Furthermore, following the consumption of SCM, c-Fos expression was increased in
magnocellular oxytocin neurons of the hypothalamic supraoptic and paraventricular
nucleus. I demonstrated that the oxytocin system was activated by gut-brain
signalling potentially involving the nucleus of the solitary tract. Therefore, the
oxytocin system may be involved in homeostatic compensatory mechanisms
triggered in response to the hedonic consumption of SCM, as part of a pathway
mediating satiety.
Moreover, I showed that c-Fos expression was also increased in the hypothalamic
supramammillary nucleus (SuM) following the consumption of SCM. It has been
previously shown that the SuM is involved in reward-related motivated behaviours
and was recently implicated in the motivation to acquire and consume palatable food
rewards. I also demonstrated that c-Fos expression in the SuM might be specific to
the motivated consumption of palatable food, consistent with the SuM being
involved in reward-related motivated behaviours. Furthermore, there is additional
evidence from these studies that the SuM may functionally communicate with brain
regions in the homeostatic and hedonic systems, including the lateral hypothalamus,
dorsomedial hypothalamus and ventral tegmental area. Finally, I explored whether
the gut-secreted orexigenic hormone ghrelin activates the SuM, as ghrelin may act
at the SuM to influence feeding motivation. However, systemic ghrelin administration
did not influence SuM c-Fos expression. As the SuM is activated following the
consumption of SCM and may act as an interface between the homeostatic and
hedonic systems, it is possible that the SuM could be a key component in the
regulation of hedonic feeding.
Using a rat model, I have shown that homeostatic compensatory mechanisms are
triggered in response to the hedonic consumption of palatable, high-sugar food to
regulate energy intake. This response is likely to involve homeostatic satiety
mechanisms and interactions between multiple brain regions involved in the
homeostatic and hedonic control of food intake. Overall, these findings shed light on
how the homeostatic system responds to hedonic energy consumption and
highlights specific brain regions that may be involved in hedonic feeding or
homeostatic compensatory responses
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