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Involvement of cocaine-amphetamine regulated transcript in the differential feeding responses to nociceptin/orphanin FQ in dark agouti and Wistar Ottawa Karlsburg W rats
Full text linkWistar Ottawa Karlsburg W (WOKW) rats and their controls, dark agouti (DA), present different features: in particular, DA rats are lean, while the WOKW are obese and present symptoms of hypertension, dyslipidemia, hyperinsulinemia, and impaired glucose tolerance. The present study tested the hypothesis that these two strains would demonstrate different sensitivity to nociceptin/orphanin FQ (N/OFQ). N/OFQ was injected into the lateral brain ventricle (LBV) of sated DA and WOKW rats, and corticosterone levels in both strains were measured after LBV injection of N/OFQ. LBV N/OFQ injections dose-dependently produced a significant increase in food intake (4 h) in DA rats, but not in WOKW. However, corticosterone levels were increased by N/OFQ to a greater degree in WOKW than in DA rats. Gene sequencing and gene expression of ORL1 receptor and cocaine-amphetamine regulated transcript (Cart) peptide were evaluated to study the difference in N/OFQ-induced feeding behavior in the two strains. WOKW rats had a different amino acid sequence of Cart peptide and a significantly higher expression of Cart in the hypothalamus. The present data show that DA and WOKW rats demonstrate different sensitivity to N/OFQ, and suggest that Cart peptide might be the underlying mechanism of this difference
Nociceptin/orphanin FQ-induced food intake and cocaine amphetamine regulated transcript gene expression in strains derived from rats prone (WOKW) and resistant (Dark Agouti) to metabolic syndrome
Full text linkIn previous work, we observed that N/OFQ-induced hyperphagia is greater in DA rats, animals resistant to metabolic syndrome, than in WOKW animals, which are prone to this disease. We attributed this difference to the fact that these two strains have different Cart gene sequences and expression. As a preliminary approach to pursue this hypothesis, the present work focused on Cart gene expression by developing from DA and WOKW rats various congenic animals with exchanges of metabolic syndrome-related QTL's of different chromosomes (3, 5, 10 and 16), and analyzing their N/OFQ-induced (2.1, 4.2, and 8.4nmol/rat) food intake in terms of their CART gene expression and N/OFQ hypothalamic immunostaining. Two groupings emerged, the first, with strains 3a, 3b, and 5a with elevated N/OFQ-induced feeding similar to that of the DA rats, and the second, with strains 16 and 10, with lower feeding, like the WOKW rats. There was a perfect correlation between Cart gene expression and N/OFQ-induced feeding data at 30min for the strains DA, 3a, 3b, 5 in the first group, and 16 and WOKW for the second, but not for strain 10. As expected, the strains with low content of Cart gene expression had elevated N/OFQ-induced feeding, but contrary to expectations, strain 10, with the lowest Cart gene expression, exhibited low N/OFQ-induced feeding, on the order of that of the WOKW rats. A comparable trend was observed with N/OFQ hypothalamic immunostaining. This anomaly may be due to other satiety-related factors involved in N/OFQ-induced feeding
Gender differences in Nociceptin/ Orphanin FQ-induced food intake in strains derived from rats prone (WOKW) and resistant (Dark Agouti) to metabolic syndrome: a possible involvement of the cocaine- and amphetamine-regulated transcript system.
No full textOur previous study found that when injected
with Nociceptin/Orphanin FQ (N/OFQ) into the brain,
male Dark Agouti (DA) rats, which are resistant to metabolic
syndrome, have greater hyperphagia than male Wistar
Ottawa Karlsburg W(WOKW) animals, which are prone to
this disease. We attributed this difference to the fact that
these two strains have different cocaine-amphetamine
regulated transcript peptide (Cart) gene sequences and
expression. In order to address this hypothesis, the present
work focused on sex differences and analyzed not only
male but also female N/OFQ-induced (0.25 and 0.5 nmol/
rat) food intake in terms of their Cart and N/OFQ receptor
gene expression in the hypothalamic area. In N/OFQ-naive
WOKW females, cart gene expression is extremely elevated
compared to N/OFQ-naive WOKW males. When
male and female WOKW littermates are stimulated with
N/OFQ, the food intake of females is significantly lower
than that of the males. Granted, the N/OFQ feeding
behavior experiments were not performed on the animals
measured for Cart gene expression, but nonetheless, the
responses observed in littermates point to an interesting
avenue for further inquiry
Stress response of pancreatic islets from diabetes prone BB rats of different age
No full textProtective and/or repair mechanisms are thought to be activated in pancreatic beta cells in response to injury during insulitis. Manifestation of type-1 diabetes may depend on an imbalance between beta cell damage and repair. To prove this hypothesis, the ability of collagenase-isolated islets to respond to heat stress depending on the age of BB rats was investigated. The islets were exposed either to 44degreesC (HS) or 37degreesC (control) for 30 min and then kept at 37degreesC for 5 h. Immediately and 5 h after heat shock, insulin secretion in response to 20 mmol/l glucose and total protein synthesis of heat-exposed islets were significantly diminished as compared with controls. The islet proteins were separated by SDS-PAGE followed by immunoblotting. Islets from BB rats at an age of 6-90 days responded to heat shock with the expression of major heat shock protein 70 (HSP 70). Islets from 3-day old rats, however, did not respond with induction of HSP 70. In contrast we could detect inducible HSP 70 in islets from 3-day old diabetes-resistant LEW rats. In islets from 90-day old BB rats we observed a decreased amount of HSP 70 compared with islets from 9-, 12-, 30- and 60-day old animals. There was also a higher extent of HSP 70 to observe in islets from 90-day old LEW rats as compared with 90-day old BB rats. Differences in HSP 70 expression between islets of 3-day old BB and LEW rats and other age groups of BB rats might represent distinct stages of maturation of islets whereas diminished expression of HSP 70 in islets of 90-day old BB rats at the age of high probability of developing diabetes might result from reduced ability to induce protective mechanisms
The hyperphagic effects of Nociceptin/Orfanin FQ (N/OFQ) in obese and lean rats and their congenic offspring: relation to expression of N/OFQ-NOP receptors in the hypothalamus and their genoma
No full textNociceptin/orphanin FQ (N/OFQ) has been shown to produce hyperphagia when injected into the brain of normal rats. Rats with the metabolic syndrome, such as the WOKW rats, exibit lower hyperphagic effects following central injection of N/OFQ when compared to lean counterparts such as the dark agouti (DA) rats. Crossing between WOKW and DA rats has generated several congenic lines of rats the chromosomal differences of which have been fully characterized. DA.WOKW rats were the offspring of a cross of WOKW and DA rats using marker-aided selection. The resulting cross hybrids were repeatedly backcrossed with DA using animals which were heterozygous at loci D3Mgh5, D3Rat1 (DA.3Wa) or D3Mit10, D3Rat189 (DA.3Wb) or D5Mgh6, D5Mit5 (DA.5W) or D9Mgh1, D16Rat89 (DA.16W) and were most homozygous for DA alleles at 180 background loci. After 5 backcross generations, the animals were inter-crossed. Animals homozygous for WOKW alleles at the loci of interest were selected and the congenic DA.3Wa, DA.3Wb, DA.5W and DA.16W rat strains were founded. Founder animals were fine mapped with more than 30 polymorphic markers on chromosomes 3, 5, and 16, chromosomes very important in the expression of diabetes and obesity.The present work evaluated the hyperphagic effect of N/OFQ in all these lines and the location of NOP receptor and N/OFQ into the hypothalamus of WOKW and DA rats using immunohistochemistry. Six males of each congenic strain and DA as well as WOKW rats were injected into the lateral brain ventricle with N/OFQ (2.1, 4.2, 8.4 nmol/rat) and their feeding responses were measured for the following 2h. DA, DA.5W, DA.3Wb significantly dose-dependently increased their food intake after N/OFQ injection. On the other hand, WOKW, and DA.16W rats did not show any significant increase in food intake. Immunoreactivity to N/OFQ was seen in the arcuate nucleus, ventromedial nucleus and dorsomedial nucleus. Staining was intense and present in both neurons and fibers. NOP receptor immunoreactivity was found in fibers only. Staining was low to moderate in ventromedial nucleus and dorsomedial nucleus, and strongly positive in the median eminence. No significant differences emerged by comparing WOKW and DA rats.The exchange of a region on chromosomes 3b and 5, but not in chromosome 16 significantly produced alteration of feeding in these animals. Therefore, these resistant WOKW and chromosome 16 congenic animals could help to identify the genes controlling N/OFQ-induced hyperphagia
The hyperphagic effects of nociceptin/orfanin FQ(N/OFQ) in obese and lean rats and their congenic offsring: relation to expression of N/OFQ-NOP receptors in the hypothalamus and their genoma
No full text
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
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