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- Philippot, Gaetan, et al.
(författare)
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A Cannabinoid Receptor Type 1 (CB1R) Agonist Enhances the Developmental Neurotoxicity of Acetaminophen (Paracetamol)
- 2018
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Ingår i: Toxicological Sciences. - : OXFORD UNIV PRESS. - 1096-6080 .- 1096-0929. ; 166:1, s. 203-212
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Tidskriftsartikel (refereegranskat)abstract
- Acetaminophen (AAP; also known as paracetamol) is the most used and only recommended analgesic and antipyretic among pregnant women and young children. However, recent findings in both humans and rodents suggest a link between developmental exposure to AAP and adverse neurobehavioral effects later in life. We hypothesized that the cannabinoid receptor type 1 (CB1R) may be involved in the developmental neurotoxicity of AAP, owing to its interaction with the endocannabinoid system. Here we test if CB1R agonist WIN 55 212-2 (WIN) and AAP can interact when exposure occurs during a neurodevelopmental stage known for increased growth rate and for its vulnerability to AAP exposure. We exposed male NMRI mice on postnatal day 10 to different combinations of AAP and WIN. Adult mice, neonatally co-exposed to AAP and WIN, displayed a significant lack of habituation in the spontaneous behavior test, when compared with controls and single agent exposed mice. These adult adverse effects may at least in part be explained by a reduction of transcript levels of hippocampal synaptophysin (Syp) and tropomyosin receptor kinase B (Trkb), and cerebral cortical fatty acid amide hydroxylase (Faah), 24h after exposure. These findings are consistent with our hypothesis that AAP and WIN can interact when exposure occurs during early postnatal brain development in mice. Assuming our results are relevant for humans, they raise concerns on AAP safety because it is the only recommended analgesic and antipyretic during pregnancy and early life.
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| 5. |
- Bagchi, Sonchita, et al.
(författare)
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In Situ Proximity Ligation Assay (PLA)
- 2015
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Ingår i: ELISA. - New York, NY : Springer-Verlag New York. - 9781493927425 - 9781493927418 ; , s. 149-159
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Bokkapitel (refereegranskat)abstract
- In situ proximity ligation assay (PLA) is a method to identify physical closeness of proteins, where a signal will only be produced if the two proteins are closer than 40 nm, in tissue section or cell cultures. Modifications of the PLA method can also be used to increase specificity or sensitivity of standard immunohistochemistry protocols.
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| 6. |
- Bäckström, Daniel, 1985, et al.
(författare)
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On the use of alternative fuels in rotary kiln burners - An experimental and modelling study of the effect on the radiative heat transfer conditions
- 2015
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Ingår i: Fuel processing technology. - : Elsevier. - 0378-3820 .- 1873-7188. ; 138, s. 210-220
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Tidskriftsartikel (refereegranskat)abstract
- Abstract In this work, the radiative heat transfer conditions in a 400 kWfuel test furnace were studied. The test furnace is a scaled pilot of a rotary kiln furnace used in iron ore pellet production. In particular, the study focuses on the choice of fuel and the subsequent effect on temperature and radiative conditions in the flame. Several co-firing flames of coal and biomass were investigated and also other fuels such as heavy fuel oil and natural gas. The test furnace was used in the experiments, and radiative intensity was measured with a narrow angle radiometer. Detailed radiation modelling was performed using spectral models for gas and particle properties. The results show that all co-firing flames give a shorter radiating flame length. Based on the radiation modelling, it was also shown that the particle radiation dominates the heat transfer from the flames. Due to the high pre-heating temperature of the combustion air (1100°C), the flame temperatures were generally very high. The flame temperature in the natural gas flame was likely around 2000°C while the coal flame temperatures were estimated to 1500-1600°C. The two coals tested, having almost identical fuel specifications, resulted in a substantial difference in the radiation intensity emitted by the flame. This emphasizes the need of direct radiation measurements to evaluate fuel changes in industrial processes that are highly dependent on the heat transfer conditions.
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| 7. |
- Caruso, Vanni, et al.
(författare)
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mRNA GPR162 changes are associated with decreased food intake in rat, and its human genetic variants with impairments in glucose homeostasis in two Swedish cohorts
- 2016
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Ingår i: Gene. - : Elsevier BV. - 0378-1119 .- 1879-0038. ; 581:2, s. 139-145
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Tidskriftsartikel (refereegranskat)abstract
- G protein-coupled receptors (GPCRs) are a class of integral membrane proteins mediating intercellular interactions of fundamental physiological importance for survival including regulation of food intake, blood pressure, and hormonal sensing signaling, among other roles. Homeostatic alterations in the physiological status of GPCRs are often associated with underlying causes of disease, and to date, several orphan GPCRs are still uncharacterized. Findings from our previous study demonstrate that the Rhodopsin family protein GPR162 is widely expressed in GABAergic as well as other neurons within the mouse hippocampus, whereas extensive expression is observed in hypothalamus, amygdala, and ventral tegmental area, regions strictly interconnected and involved in the regulation of energy homeostasis and hedonic feeding. In this study, we provide a further anatomical characterization of GPR162 in mouse brain via in situ hybridization as well as detailed mRNA expression in a panel of rat tissues complementing a specie-specific mapping of the receptor. We also provide an attempt to demonstrate a functional implication of GPR162 in food intake-related behavior via antisense knockdown studies. Furthermore, we performed human genetic studies in which for the first time, variants of the GPR162 gene were associated with impairments in glucose homeostasis.
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| 8. |
- Caruso, Vanni, et al.
(författare)
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The Orphan G Protein-Coupled Receptor Gene GPR178 Is Evolutionary Conserved and Altered in Response to Acute Changes in Food Intake
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- G protein-coupled receptors (GPCRs) are a class of integral membrane proteins mediating physiological functions fundamental for survival, including energy homeostasis. A few years ago, an amino acid sequence of a novel GPCR gene was identified and named GPR178. In this study, we provide new insights regarding the biological significance of Gpr178 protein, investigating its evolutionary history and tissue distribution as well as examining the relationship between its expression level and feeding status. Our phylogenetic analysis indicated that GPR178 is highly conserved among all animal species investigated, and that GPR178 is not a member of a protein family. Real-time PCR and in situ hybridization revealed wide expression of Gpr178 mRNA in both the brain and periphery, with high expression density in the hypothalamus and brainstem, areas involved in the regulation of food intake. Hence, changes in receptor expression were assessed following several feeding paradigms including starvation and overfeeding. Short-term starvation (12-48h) or food restriction resulted in upregulation of Gpr178 mRNA expression in the brainstem, hypothalamus and prefrontal cortex. Conversely, short-term (48h) exposure to sucrose or Intralipid solutions downregulated Gpr178 mRNA in the brainstem; long-term exposure (10 days) to a palatable high-fat and high-sugar diet resulted in a downregulation of Gpr178 in the amygdala but not in the hypothalamus. Our results indicate that hypothalamic Gpr178 gene expression is altered during acute exposure to starvation or acute exposure to palatable food. Changes in gene expression following palatable diet consumption suggest a possible involvement of Gpr178 in the complex mechanisms of feeding reward.
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| 9. |
- Ceder, Mikaela, et al.
(författare)
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The Neuronal and Peripheral Expressed Membrane-Bound UNC93A Respond to Nutrient Availability in Mice
- 2017
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Ingår i: Frontiers in Molecular Neuroscience. - : FRONTIERS MEDIA SA. - 1662-5099. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Many transporters such as the solute carriers belonging to the Major facilitator superfamily Pfam clan are orphans in that their tissue and cellular localization as well as substrate profile and function are still unknown. Here we have characterized the putative solute carrier UNC93A. We aimed to investigate the expression profile on both protein and mRNA level of UNC93A in mouse since it has not been clarified. UNC93A staining was found in cortex, hippocampus and cerebellum. It was found to be expressed in many neurons, but not all, with staining located in close proximity to the plasma membrane. Furthermore, we aimed to extend the starvation data available for Unc93a in hypothalamic cell cultures from mouse. We investigated the Unc93a alterations with focus on amino acid deprivation in embryonic cortex cells from mice as well as 24 h starvation in adult male mice and compared it to recently studied putative and known solute carriers. Unc93a expression was found both in the brain and peripheral organs, in low to moderate levels in the adult mice and was affected by amino acid deprivation in embryonic cortex cultures and starvation in in vivo samples. In conclusion, the membrane-bound UNC93A is expressed in both the brain and peripheral tissues and responds to nutrient availability in mice.
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| 10. |
- Corell, Mikael, et al.
(författare)
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GABA and its B-receptor are present at the node of Ranvier in a small population of sensory fibers, implicating a role in myelination
- 2015
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Ingår i: Journal of Neuroscience Research. - : Wiley. - 0360-4012 .- 1097-4547. ; 93:2, s. 285-295
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Tidskriftsartikel (refereegranskat)abstract
- The γ-aminobutyric acid (GABA) type B receptor has been implicated in glial cell development in the peripheral nervous system (PNS), although the exact function of GABA signaling is not known. To investigate GABA and its B receptor in PNS development and degeneration, we studied the expression of the GABAB receptor, GABA, and glutamic acid decarboxylase GAD65/67 in both development and injury in fetal dissociated dorsal root ganglia (DRG) cell cultures and in the rat sciatic nerve. We found that GABA, GAD65/67, and the GABAB receptor were expressed in premyelinating and nonmyelinating Schwann cells throughout development and after injury. A small population of myelinated sensory fibers displayed all of these molecules at the node of Ranvier, indicating a role in axon-glia communication. Functional studies using GABAB receptor agonists and antagonists were performed in fetal DRG primary cultures to study the function of this receptor during development. The results show that GABA, via its B receptor, is involved in the myelination process but not in Schwann cell proliferation. The data from adult nerves suggest additional roles in axon-glia communication after injury.
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