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Sympathetic stimulation with norepinephrine may come at a cost

Neural Regeneration Research 2019年第6期14卷 977-978页

作者： Lakshini Y.Herat Markus P.Schlaich Vance B.Matthews dobney hypertension centre School of Biomedical Science-Royal Perth Hospital UnitUniversity of Western Australia dobney hypertension centre School of Medicine - Royal Perth Hospital UnitUniversity of Western Australia Department of Cardiology and Department of Nephrology Royal Perth Hospital

Norepinephrine(NE;also known as noradrenaline)is the body’s primary adrenergic neurotransmitter which belongs to the catecholamine *** has pharmacologic effects on theα1(Suita et al.,2015),α2(Schwartz,1997),β1,β2 andβ3(Tsukada et al.,2003)*** the brain,norepinephrine increases arousal and alertness,promotes vigilance,enhances formation and retrieval of memory,and focuses *** also increases restlessness and *** the remainder of the body,norepinephrine increases heart rate and blood pressure,triggers the release of glucose from energy stores,increases blood flow to skeletal muscle and increases muscle contraction,reduces blood flow to the gastrointestinal system and its motility and lastly,inhibits voiding of the bladder(Goldstein,2010).This last point is particularly interesting in the context of this perspective piece.

关键词： neurotransmitter norepinephrine increases focuses attention

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The Schlager mouse as a model of altered retinal phenotype

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Neural Regeneration Research 2020年第3期15卷 512-518页

作者： Lakshini Y.Herat Aaron L.Magno Márcio G.Kiuchi Kristy L.Jackson Revathy Carnagarin Geoffrey A.Head Markus P.Schlaich Vance B.Matthews dobney hypertension centre School of Biomedical Science-Royal Perth Hospital UnitUniversity of Western AustraliaPerthAustralia Research centre Royal Perth HospitalPerthAustralia dobney hypertension centre School of Medicine-Royal Perth Hospital UnitUniversity of Western AustraliaPerthAustralia Neuropharmacology Laboratory Baker Heart and Diabetes InstituteMelbourneAustralia Department of Cardiology and Department of Nephrology Royal Perth HospitalPerthAustralia

hypertension is a risk factor for a large number of vision-threatening eye *** this study,we investigated for the first time the retinal neural structure of the hypertensive BPH/2J mouse(Schlager mouse)and compared it to its control counterpart,the normotensive BPN/3J *** BPH/2J mouse is a selectively inbred mouse strain that develops chronic hypertension due to elevated sympathetic nervous system *** compared to the BPN/3J strain,the hypertensive BPH/2J mice showed a complete loss of outer layers of the neural retina at 21 weeks of age,which was indicative of a severe vision-threatening disease potentially caused by *** elucidate whether the retinal neural phenotype in the BPH/2J strain was attributed to increased BP,we investigated the neural retina of both BPN/3J and BPH/2J mice at 4 weeks of *** preliminary results showed for the first time that the BPH/2J strain develops severe retinal neural damage at a young *** findings suggest that the retinal phenotype in the BPH/2J mouse is possibly due to elevated blood pressure and may be contributed by an early onset spontaneous mutation which is yet to be identified or a congenital defect occurring in this *** characterization of the BPH/2J mouse strain is likely to i)elucidate gene defects underlying retinal disease;ii)understand mechanisms leading to neural retinal disease and iii)permit testing of molecules for translational research to interfere with the progression of retinal *** animal experiments were performed with the approval of the Royal Perth Hospital Animal Ethics Committee(R535/17-18)on June 1,2017.

关键词： blood pressure eye hypertension mice neural regeneration retina Schlager mouse sympathetic nervous system

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Sodium glucose co-transporter 2 inhibition reduces succinate levels in diabetic mice

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World Journal of Gastroenterology 2020年第23期26卷 3225-3235页

作者： Lakshini Y Herat Natalie C Ward Aaron L Magno Elizabeth P Rakoczy Marcio G Kiuchi Markus P Schlaich Vance B Matthews School of Biomedical Sciences Dobney Hypertension CentreRoyal Perth Hospital UnitUniversity of Western AustraliaPerth 6000Australia Faculty of Health and Medical Sciences University of Western AustraliaCrawley 6009Australia Faculty of Health Sciences School of Public HealthCurtin UniversityBentley 6102Australia Research centre Royal Perth HospitalPerth 6000Australia Department of Molecular Ophthalmology University of Western AustraliaCrawley 6009Australia dobney hypertension centre School of MedicineRoyal Perth Hospital UnitUniversity of Western AustraliaPerth 6000Australia Department of Cardiology and Department of Nephrology Royal Perth HospitalPerth 6000Australia

BACKGROUND Type 1 diabetes(T1D) is associated with major chronic microvascular complications which contribute significantly to diabetes associated *** protein primarily responsible for glucose reabsorption in the kidney is sodium glucose co-transporter 2(SGLT2). Presently, SGLT2 inhibitors are widely used in diabetic patients to improve blood glucose levels and prevent cardiovascular and renal complications. Given the broad therapeutic application of SGLT2 inhibitors, we hypothesised that SGLT2 inhibition may exert its protective effects via alterations of the gut microbiome and tested this in a type 1 diabetic mouse model of diabetic *** To determine whether the treatment with two independent SGLT2 inhibitors affects gut health in a type 1 diabetic mouse *** The SGLT2 inhibitors empagliflozin or dapagliflozin(25 mg/kg/d) or vehicle dimethylsulfoxide(DMSO) were administered to C57 BL/6 J, Akita, Kimba and Akimba mice at 10 wk of age for 8 wk via their drinking water. Serum samples were collected and the concentration of succinate and the short chain fatty acid(SCFA) butyric acid was measured using gas chromatography-mass spectrometry. Enzyme-linked immunosorbent assay(ELISA) was performed to determine the concentration of insulin and leptin. Furthermore, the norepinephrine content in kidney tissue was determined using ELISA. Pancreatic tissue was collected and stained with haematoxylin and eosin and analysed using brightfield *** Due to the presence of the Akita allele, both Akita and Akimba mice showed a reduction in insulin production compared to C57 BL/6 J and Kimba ***, Akita mice also showed the presence of apoptotic bodies within the pancreatic islets. The acinar cells of Akita and Akimba mice showed swelling which is indicative of acute injury or pancreatitis. After 8 wk of SGLT2 inhibition with dapagliflozin, the intermediate metabolite of gut metabolism known as succinate was significantly reduced

关键词： Sodium glucose co-transporter inhibitors Sodium glucose co-transporter 2 Diabetes Diabetic retinopathy Mouse Gut microbiota Empagliflozin Dapagliflozin Succinate Akimba

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