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- Lee, S. J., et al.
(författare)
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Blunted Vagal Cocaine- and Amphetamine-Regulated Transcript Promotes Hyperphagia and Weight Gain
- 2020
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 30:6
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Tidskriftsartikel (refereegranskat)abstract
- The vagus nerve conveys gastrointestinal cues to the brain to control eating behavior. In obesity, vagally mediated gut-brain signaling is disrupted. Here, we show that the cocaine- and amphetamine-regulated transcript (CART) is a neuropeptide synthesized proportional to the food consumed in vagal afferent neurons (VANs) of chow-fed rats. CART injection into the nucleus tractus solitarii (NTS), the site of vagal afferent central termination, reduces food intake. Conversely, blocking endogenous CART action in the NTS increases food intake in chow-fed rats, and this requires intact VANs. Viral-mediated Cartpt knockdown in VANs increases weight gain and daily food intake via larger meals and faster ingestion rate. In obese rats fed a high-fat, high-sugar diet, meal-induced CART synthesis in VANs is blunted and CART antibody fails to increase food intake. However, CART injection into the NTS retains its anorexigenic effect in obese rats. Restoring disrupted VAN CART signaling in obesity could be a promising therapeutic approach.
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- Singh, A., et al.
(författare)
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Demystifying functional role of cocaine- and amphetamine-related transcript (CART) peptide in control of energy homeostasis: A twenty-five year expedition
- 2021
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781. ; 140
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Tidskriftsartikel (refereegranskat)abstract
- Cocaine- and amphetamine-related transcript (CART) is a neuropeptide first discovered in the striatum of the rat brain. Later, the genetic sequence and function of CART peptide (CARTp) was found to be conserved among multiple mammalian species. Over the 25 years, since its discovery, CART mRNA (Cartpt) expression has been reported widely throughout the central and peripheral nervous systems underscoring its role in diverse physiological functions. Here, we review the localization and function of CARTp as it relates to energy homeostasis. We summarize the expression changes of central and peripheral Cartpt in response to metabolic states and make use of available large data sets to gain additional insights into the anatomy of the Cartpt expressing vagal neurons and their expression patterns in the gut. Furthermore, we provide an overview of the role of CARTp as an anorexigenic signal and its effect on energy expenditure and body weight control with insights from both pharmacological and transgenic animal studies. Subsequently, we discuss the role of CARTp in the pathophysiology of obesity and review important new developments towards identifying a candidate receptor for CARTp signalling. Altogether, the field of CARTp research has made rapid and substantial progress recently, and we review the case for considering CARTp as a potential therapeutic target for stemming the obesity epidemic.
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- Basini, M., et al.
(författare)
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Low-temperature anomalies in muon spin relaxation of solid and hollow gamma-Fe2O3 nanoparticles : A pathway to detect unusual local spin dynamics
- 2020
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Ingår i: Physical Review B. - : American Physical Society (APS). - 2469-9950 .- 2469-9969. ; 102:19
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Tidskriftsartikel (refereegranskat)abstract
- By means of muon spin relaxation measurements we unraveled the temperature spin dynamics in monodisperse maghemite spherical nanoparticles with different surface to volume ratio, in two samples with a full core (diameter D similar to 4 and D similar to 5 nm) and one with a hollow core (external diameter D similar to 7.4 nm). The behavior of the muon longitudinal relaxation rates as a function of temperature allowed us to identify two distinct spin dynamics. The first is well witnessed by the presence of a characteristic peak for all the samples around the so-called muon blocking temperature T-B(mu+). A Bloembergen-Purcell-Pound (BPP)-like model reproduces the experimental data around the peak and at higher temperatures (20 < T < 100 K) by assuming the Neel reversal time of the magnetization as the dominating correlation time. An additional dynamic emerges in the samples with higher surface to volume ratio, namely, full 4 nm and hollow samples. This is witnessed by a shoulder of the main peak for T < 20 K at low longitudinal field (mu H-0 approximate to 15 mT), followed by an abrupt increase of the relaxation rate at T < 10 K, which is more evident for the hollow sample. These unusual anomalies of the longitudinal relaxation rate for T < T-B(mu+) are suggested to be due to the surface spins' dynamical behavior. Furthermore, for weak applied longitudinal magnetic field (mu H-0 approximate to 15 mT) and T < T-B(mu+) we observed damped coherent oscillations of the muon asymmetry, which are a signature of a quasistatic local field at the muon site as probed by muons implanted in the inner magnetic core of the nanoparticles. The muon spin relaxation technique turns out to be very successful to study the magnetic behavior of maghemite nanoparticles and to detect their unusual local spin dynamics in low magnetic field conditions.
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- Krieger, Jean-Philippe, et al.
(författare)
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Neural Pathway for Gut Feelings: Vagal Interoceptive Feedback From the Gastrointestinal Tract Is a Critical Modulator of Anxiety-like Behavior
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223. ; 92:9, s. 709-721
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Anxiety disorders are associated with an altered perception of the body's internal state. Therefore, understanding the neuronal basis of interoception can foster novel anxiety therapies. In rodents, the feeding status bidirectionally modulates anxiety-like behavior but how the sensing of gastrointestinal state affects anxiety remains unclear.METHODS: We combined chemogenetics, neuropharmacology, and behavioral approaches in male and female rats to test whether vagal afferents terminating in the gastrointestinal tract mediate feeding-induced tuning of anxiety. Using saporin-based lesions and transcriptomics, we investigated the chronic impact of this gut-brain circuit on anxiety-like behavior.RESULTS: Both feeding and selective chemogenetic activation of gut-innervating vagal afferents increased anxiety -like behavior. Conversely, chemogenetic inhibition blocked the increase in anxiety-like behavior induced by feeding. Using a selective saporin-based lesion, we demonstrate that the loss of gut-innervating vagal afferent signaling chronically reduces anxiety-like behavior in male rats but not in female rats. We next identify a vagal circuit that connects the gut to the central nucleus of the amygdala, using anterograde transsynaptic tracing from the nodose ganglia. Lesion of this gut-brain vagal circuit modulated the central amygdala transcriptome in both sexes but selectively affected a network of GABA (gamma-aminobutyric acid)-related genes only in males, suggesting a potentiation of inhibitory control. Blocking GABAergic signaling in the central amygdala re-established normal anxiety levels in male rats. CONCLUSIONS: Vagal sensory signals from the gastrointestinal tract are critical for baseline and feeding-induced tuning of anxiety via the central amygdala in rats. Our results suggest vagal gut-brain signaling as a target to normalize interoception in anxiety disorders.
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