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Wake-sleep, thermoregulatory, and autonomic effects of cholinergic activation of the lateral hypothalamus in the rat: a pilot study
No full textA major role in the wake-promoting effects of the activation of the lateral hypothalamus (LH) has been ascribed to a population of orexin (ORX)-containing neurons that send projections to central areas which regulate Wake-Sleep and autonomic function. Since, in the rat, a substantial amount of ORX neurons receive cholinergic projections from cells involved in Wake-Sleep regulation, the aim of this study was to assess the role played by LH cholinoceptive cells in Wake-Sleep and autonomic regulations. To this end, the effects of a microinjection of the cholinergic agonist Carbachol (CBL) into the LH were compared to those obtained through the activation of a wider cell population by the microinjection of the GABAA antagonist GABAzine (GBZ). The results of this pilot study showed that both drugs elicited the same behavioral and autonomic effects, those caused by GBZ being larger and longer-lasting than those following administration of CBL. Briefly, wakefulness was enhanced and sleep was depressed, and brain temperature and heart rate consistently increased, while mean arterial pressure showed only a mild increment. Surprisingly, the administration of the drug vehicle (SAL) elicited a similar pattern of Wake-Sleep effects which, although much smaller, were sufficient to mask any statistical significance between treatment and control data. In conclusion, the results of this work show that the arousal elicited by LH disinhibition by GABAzine is concomitant with autonomic responses set by the intervention of cold-defense mechanisms. Since the same response is elicited at a lower level by CBL administration, the hypothesis of an involvement of cholinoceptive ORX neurons in its generation is discussed
Cellular and systemic aspects of the activation and inhibition of the Raphe Pallidus neurons
Full text linkScopo della tesi è stato studiare nel ratto libero di muoversi i correlati comportamentali (modificazione degli stati veglia/sonno, assunzione di cibo) e della funzionalità cellulare nervosa centrale della manipolazione farmacologica locale del Raphe Pallidus (RPa), area sede di pre-motoneuroni simpatici che regolano processi inerenti la termogenesi.
Studi precedenti hanno mostrato, da un lato, che l’iniezione di Oressina A (ORXA) nel ratto a livello del RPa induce un aumento della temperatura cerebrale e della pressione arteriosa, ma solo in presenza di un drive termogenico in atto, indotto dall’esposizione a una temperatura ambientale (Ta) sub-termoneutrale. Dall’altro lato, è stato invece osservato che l’inibizione del RPa, mediante iniezione di un agonista GABA-ergico (muscimolo, MUS), determina nel ratto, specie non-ibernante, un blocco della termogenesi inducendo uno stato ipotermico di pseudo torpore e un’ampia riduzione dell'attività elettrica corticale.
I risultati della tesi mostrano che l’iniezione di ORXA nel RPa a una Ta di 24°C, di poco inferiore al valore termoneutrale, induce un ampio e protratto aumento della veglia e un significativo aumento dell’assunzione di cibo. Gli effetti risveglianti sono meno intensi e l’assunzione di cibo non diversa da quella dei controlli dopo iniezione dell’antagonista GABA-ergico GABA-zina o di ORXA a Ta 32°C. Un’indagine immunoistochimica condotta per verificare se tali effetti comportamentali fossero legati a un’attivazione dei neuroni serotoninergici del RPa ha dato risultati negativi.
Nel secondo esperimento, gli effetti indotti dall’ipotermia che segue un inibizione del RPa con MUS sull’attività cellulare di aree cerebrali che regolano processi di vigilanza e funzione autonomica sono stati valutati attraverso lo studio immunoistochimico della proteina Tau, della quale è stata osservata un’iperfosforilazione reversibile indotta dal torpore in specie ibernanti. I risultati ottenuti hanno mostrato nel ratto un andamento analogo a quello dell’ibernante naturale, suggerendo che l’iperfosforilazione Tau sia un meccanismo generalizzato di difesa dall’ipotermia della funzione cellulare nervosa.Aim of this thesis was to assess, in the free behaving rat, the behavioral (wake/sleep states, food intake) and, at a brain level, cellular correlates of the local pharmacological manipulation of the Raphe pallidus (RPa), a brainstem area containing premotor sympathetic neurons regulating thermogenesis.
Previous studies have shown that OrexinA (ORXA) injection in the RPa of rats induces an increase in brain temperature and blood pressure, but only in the presence of a thermogenic drive induced by the exposure to a sub-thermoneutral ambient temperature (Ta). Also, the inhibition of RPa in the rat (a non-hibernating species), through the injection of the GABA-ergic agonist (muscimol, MUS) promotes a block of thermogenesis inducing a hypothermic torpor-like state and a large decrease in cortical activity.
The results shown in this thesis indicate that ORXA injection in RPa at Ta 24°C, slightly below the thermoneutral range, induces a large and sustained increase in wakefulness and a significant increase in food intake. The wake promoting effects are less intense and the food intake is not different from that of controls, after the injection of either the GABA-ergic antagonist GABA-zine or ORXA at Ta 32°C. An immunohistochemical study aimed at assessing whether these behavioural effects were due to an activation of serotonergic neurons in the RPa gave negative results.
In the second experiment, the effects on cell function of the hypothermia which followed the inhibition of RPa by MUS were assessed in brain areas that regulate wake/sleep processes and autonomic function by an immunohistochemical study of Tau protein activity, since Tau has been shown to be reversibly hyperphosphorylated during torpor in hibernating species. The results showed a phosphorylation trend, in the rat, which resembled that observed in natural hibernating species, suggesting that Tau hyperphosphorylation is a general defense mechanism to protect cell function during hypothermia
Wake-sleep and cardiovascular regulatory changes in rats made obese by a high-fat diet
No full textObesity is known to be associated with alterations in wake-sleep (WS) architecture and cardiovascular parameters. This study was aimed at assessing the possible influence of diet-induced obesity (DIO) on sleep homeostasis and on the WS state‐dependent levels of arterial pressure (AP) and heart rate in the rat. Two groups of age-matched Sprague-Dawley rats were fed either a high-fat hypercaloric diet, leading to DIO, or a normocaloric standard diet (lean controls) for 8 weeks. While under general anesthesia, animals were implanted with instrumentation for the recording of electroencephalogram, electromyogram, arterial pressure, and deep brain temperature. The experimental protocol consisted of 48 h of baseline, 12 h of gentle handling, enhancing wake and depressing sleep, and 36-h post-handling recovery. Compared to lean controls, DIO rats showed: i) the same amount of rapid-eye movement (REM) and non-REM (NREM) sleep in the rest period, although the latter was characterized by more fragmented episodes; ii) an increase in both REM sleep and NREM sleep in the activity period; iii) a comparable post-handling sleep homeostatic response, in terms of either the degree of Delta power increase during NREM sleep or the quantitative compensation of the REM sleep loss at the end of the 36-h recovery period; iv) significantly higher levels of AP, irrespectively of the different WS states and of the changes in their intensity throughout the experimental protocol. Overall, these changes may be the reflection of a modification in the activity of the hypothalamic areas where WS, autonomic, and metabolic regulations are known to interact
Mitochondrial respiration in rats during hypothermia resulting from central drug administration
Full text link: The ability to induce a hypothermia resembling that of natural torpor would be greatly beneficial in medical and non-medical fields. At present, two procedures based on central nervous pharmacological manipulation have been shown to be effective in bringing core body temperature well below 30 °C in the rat, a non-hibernator: the first, based on the inhibition of a key relay in the central thermoregulatory pathway, the other, based on the activation of central adenosine A1 receptors. Although the role of mitochondria in the activation and maintenance of torpor has been extensively studied, no data are available for centrally induced hypothermia in non-hibernators. Thus, in the present work the respiration rate of mitochondria in the liver and in the kidney of rats following the aforementioned hypothermia-inducing treatments was studied. Moreover, to have an internal control, the same parameters were assessed in a well-consolidated model, i.e., mice during fasting-induced torpor. Our results show that state 3 respiration rate, which significantly decreased in the liver of mice, was unchanged in rats. An increase of state 4 respiration rate was observed in both species, although it was not statistically significant in rats under central adenosine stimulation. Also, a significant decrease of the respiratory control ratio was detected in both species. Finally, no effects were detected in kidney mitochondria in both species. Overall, in these hypothermic conditions liver mitochondria of rats remained active and apparently ready to be re-activated to produce energy and warm up the cells. These findings can be interpreted as encouraging in view of the finalization of a translational approach to humans
c-Fos expression in the limbic thalamus following thermoregulatory and wake-sleep changes in the rat
No full textA cellular degeneration of two thalamic nuclei belonging to the "limbic thalamus", i.e., the anteroventral (AV) and mediodorsal (MD) nuclei, has been shown in patients suffering from Fatal Familial Insomnia (FFI), a lethal prion disease characterized by autonomic activation and severe insomnia. To better assess the physiological role of these nuclei in autonomic and sleep regulation, c-Fos expression was measured in rats during a prolonged exposure to low ambient temperature (Ta, - 10 °C) and in the first hours of the subsequent recovery period at normal laboratory Ta (25 °C). Under this protocol, the thermoregulatory and autonomic activation led to a tonic increase in waking and to a reciprocal depression in sleep occurrence, which was more evident for REM sleep. These effects were followed by a clear REM sleep rebound and by a rebound of Delta power during non-REM sleep in the following recovery period. In the anterior thalamic nuclei, c-Fos expression was (1) larger during the activity rather than the rest period in the baseline; (2) clamped at a level in-between the normal daily variation during cold exposure; (3) not significantly affected during the recovery period in comparison to the time-matched baseline. No significant changes were observed in either the MD or the paraventricular thalamic nucleus, which is also part of the limbic thalamus. The observed changes in the activity of the anterior thalamic nuclei appear, therefore, to be more specifically related to behavioral activation than to autonomic or sleep regulation
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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