ORCID Profile
0000-0002-3292-4633
Current Organisation
The University of Edinburgh
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Publisher: Elsevier BV
Date: 2011
DOI: 10.1016/J.BBR.2010.08.006
Abstract: Neurokinin-1, (NK1) receptor antagonists offer strong potential as anxiolytic drugs with few side effects. The use of the Mongolian gerbil for anxiety research offers advantages because gerbil NK1 receptors share a greater homology with human NK1 receptors than those of other rodents. Studies are needed to validate existing tests of anxiety for use with this species. This study examined the effects of two anxiolytics (buspirone and diazepam) and two anxiogenics (caffeine and FG142) on male and female gerbil behaviour in the black-white box (BWB). Diazepam was anxiolytic in males but not females. The anxiolytic effects of buspirone were apparent at the lower doses in both males and females. Higher doses resulted in sedative effects in both sexes. Caffeine produced mild anxiogenesis in females at the lowest dose, and in males at the highest dose. FG7142 was mildly anxiogenic in males and not at all in females. Findings are discussed in light of previous research. The gerbil BWB should not be used as a valid test of anxiety in its current form.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 19-09-2019
Abstract: Although studies show that diabetic kidney disease has a heritable component, searches for the genetic determinants of this complication of diabetes have had limited success. In this study, a new international genomics consortium, the JDRF funded Diabetic Nephropathy Collaborative Research Initiative, assembled nearly 20,000 s les from participants with type 1 diabetes, with and without kidney disease. The authors found 16 new diabetic kidney disease–associated loci at genome-wide significance. The strongest signal centers on a protective missense coding variant at COL4A3 , a gene that encodes a component of the glomerular basement membrane that, when mutated, causes the progressive inherited nephropathy Alport syndrome. These GWAS-identified risk loci may provide insights into the pathogenesis of diabetic kidney disease and help identify potential biologic targets for prevention and treatment. Although diabetic kidney disease demonstrates both familial clustering and single nucleotide polymorphism heritability, the specific genetic factors influencing risk remain largely unknown. To identify genetic variants predisposing to diabetic kidney disease, we performed genome-wide association study (GWAS) analyses. Through collaboration with the Diabetes Nephropathy Collaborative Research Initiative, we assembled a large collection of type 1 diabetes cohorts with harmonized diabetic kidney disease phenotypes. We used a spectrum of ten diabetic kidney disease definitions based on albuminuria and renal function. Our GWAS meta-analysis included association results for up to 19,406 in iduals of European descent with type 1 diabetes. We identified 16 genome-wide significant risk loci. The variant with the strongest association (rs55703767) is a common missense mutation in the collagen type IV alpha 3 chain ( COL4A3) gene, which encodes a major structural component of the glomerular basement membrane (GBM). Mutations in COL4A3 are implicated in heritable nephropathies, including the progressive inherited nephropathy Alport syndrome. The rs55703767 minor allele (Asp326Tyr) is protective against several definitions of diabetic kidney disease, including albuminuria and ESKD, and demonstrated a significant association with GBM width protective allele carriers had thinner GBM before any signs of kidney disease, and its effect was dependent on glycemia. Three other loci are in or near genes with known or suggestive involvement in this condition ( BMP7) or renal biology ( COLEC11 and DDR1 ). The 16 diabetic kidney disease–associated loci may provide novel insights into the pathogenesis of this condition and help identify potential biologic targets for prevention and treatment.
Publisher: Cold Spring Harbor Laboratory
Date: 19-12-2018
DOI: 10.1101/499616
Abstract: Diabetic kidney disease (DKD) is a heritable but poorly understood complication of diabetes. To identify genetic variants predisposing to DKD, we performed genome-wide association analyses in 19,406 in iduals with type 1 diabetes (T1D) using a spectrum of DKD definitions basedon albuminuria and renal function. We identified 16 genome-wide significant loci. The variant with the strongest association (rs55703767) is a common missense mutation in the collagen type IV alpha 3 chain (COL4A3) gene, which encodes a major structural component of the glomerular basement membrane (GBM) implicated in heritable nephropathies. The rs55703767 minor allele (Asp326Tyr) is protective against several definitions of DKD, including albuminuria and end-stage renal disease. Three other loci are in or near genes with known or suggestive involvement in DKD (BMP7) or renal biology ( COLEC11 and DDR1 ). The 16 DKD-associated loci provide novel insights into the pathogenesis of DKD, identifying potential biological targets for prevention and treatment.
Publisher: American Diabetes Association
Date: 27-04-2018
DOI: 10.2337/DB17-0914
Abstract: Identification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication s les, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 × 10−8) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased s le sizes will continue to provide more robust inference regarding risk variant discovery for DKD.
Publisher: Elsevier BV
Date: 05-2007
DOI: 10.1016/J.JEP.2006.12.021
Abstract: Lavender is a popular treatment for stress and mild anxiety in Europe and the USA. The present study investigated the effects of (Lavandula angustifolia Mill. (Lamiaceae)) lavender odour inhalation over 2 weeks or 24 h periods, on gerbil behaviour in the elevated plus maze in mature male and female gerbils, and compared results with the effects of diazepam (1 mg/kg) i.p. after 30 min and 2-week administration. Traditional measures of open entries showed an increasing trend over the 2 weeks exposure, whereas ethological measures indicative of anxiety stretch-attend frequency and percentage protected head-dips, were significantly lower. Exploratory behaviour, total head-dip frequency, increased after 24 h lavender and 2 weeks exposure. These results are comparable with diazepam administration. There were sex differences in protected head-dip an ethological indicator of anxiety: females showed a significant decrease in protected head-dips compared to both males and to female controls. In conclusion exposure to lavender odour may have an anxiolytic profile in gerbils similar to that of the anxiolytic diazepam. In addition, prolonged, 2-week lavender odour exposure increased exploratory behaviour in females indicating a further decrease in anxiety in this sex.
Publisher: Elsevier BV
Date: 07-2023
Publisher: Elsevier BV
Date: 12-2007
DOI: 10.1016/J.PHYSBEH.2007.06.023
Abstract: To investigate the anxiolytic effects of prolonged rose odor exposure, mature gerbils were exposed to acute (24 h), chronic (2 week) rose odor, or a no odor condition. Anxiolytic effects were assessed using the elevated plus maze and black white box. Rose odor profiles were compared with diazepam (1 mg/kg) i.p. The Jonckheere-Terpstra test was used, with the Mann-Whitney U test to examine significant group differences. In the elevated plus maze, spatiotemporal measures, altered by diazepam, were unaffected by rose oil, whereas exploration, increased (headdip frequency: acute U=100, p<0.001 chronic U=13, p<0.001). In the black white box, rose oil had anxiolytic spatiotemporal and exploratory behavior effects: latency to move from the white to the black compartment (acute U=182, p<0.01, chronic U=179, p<0.05), percentage time in the white compartment (acute U=168, p<0.01, chronic U=149, p<0.01) and exploration, rear-sniff frequency white (acute U=100, p<0.001 chronic U=99, p<0.001) increased. The percentage of time in the dark area decreased (acute U=160, p<0.01, chronic U=178, p<0.05). This anxiolytic profile strengthened after chronic exposure to rose odor, transitions between the compartments (U=167, p<0.01) and percentage of time moving around the arena (U=154, p<0.001) increased. This profile was more representative of modern anxiolytics, for ex le some serotonergic agents, rather than benzodiazepine type drugs.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Stuart J. McGurnaghan.