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Budapest - Deuterium content of water and glucose tolerance: potential role for the prevalence of affective disturbances
- 1. Deuterium content of water and glucose tolerance: potential role for the prevalence of affective disturbances U1119
- 2. Serotonin and Mood Disorders The serotonin transporter (5HTT) is implicated in mood disorders and depression 5HTT contains a gene-linked polymorphic region giving rise to a short and long allele The short allele results in lower transcriptional efficiency of the promoter
- 3. S allele associated with anxiety-related traits and susceptibility for depression Canli et al Nature Neuroscience 10, 1103 - 1109 (2007)
- 4. 5HTT S allele and depression Caspi et al Science 301 (5631): 386-389 (2003)
- 5. Generation of a model animal © The Nobel Committee for Physiology or Medicine Illustration: Annika Röh
- 6. The SERT mouse (5HTT, Slc6a4) Bengel et al Molecular Pharmacology vol. 53 no. 4 649-655 (1998) ES cells Mice
- 7. The SERT mouse (5HTT, Slc6a4) Murphy et al Nature Reviews Neuroscience 9, 85-96 (2008)
- 8. Depression rates and deuterium content of tap water Upddated from Strekalova et al Behavioural Brain Research, 277: 237 – 244 (2015)
- 9. Diabetes prevalence and deuterium content of tap water Modified from Strekalova et al Behavioural Brain Research, 277: 237 – 244 (2015) with CDC’s Division of Diabetes Translation, National Diabetes Surveillance System available at http://www.cdc.gov/diabetes/statistics
- 10. Study Design 3.5 week old 5HTT+/- mice 14 days of drug treatment control light water (CLW) deuterium content of 155 ppm light water (LW) 91 ppm deuterium Citalopram (Cit) positive control (15mg/Kg/day, via water) Behavioral tests GTT (ip 1.5 mg/g)
- 11. Modified Porsolt forced swim test Modified to test for learned helplessness and for brain plasticity triggered by stress Two 6 min sessions during 2 consecutive days Third 6 min session 120 hours after the 2nd
- 12. Modified Porsolt forced swim test Session 1 CLW LW CLW LW 0 20 40 60 80 *** Latencyoffloating,sec Session 2 CLW LW CLW LW Session 3 CLW LW CLW LW WT HET Session 1 CLW LW CLW LW 0 100 200 300 400 Durationoffloating,sec Session 2 CLW LW CLW LW Session 3 CLW LW CLW LW WT HET ** **
- 13. Effect of CLW, LW and Cit on rearing CLW LW CIT CLW LW CIT 0 20 40 60 80 WT HET * * numberofrears,n 5 min session in novel cage with fresh bedding and red lighting
- 14. Novel object exploration CLW LW CIT CLW LW CIT 0 10 20 30 WT HET * Durationofexploration,s 15 min session under 5 lux
- 15. Novel object recognition 1st day animals allowed to explore 2 objects for 15 min 2nd day new object is placed at the edge Latency to discover new object and preference is measured 1 meter
- 16. Novel object recognition CLW LW CIT CLW LW CIT 0 20 40 60 80 WT HET * objectrecognition,time%
- 17. Dark/Light Box Test for anxiety related behavior Screens anxiolytic compounds 5 min session Lit compartment intensity at 25 lux
- 18. Dark/Light Box CLW LW CIT CLW LW CIT 0 20 40 60 * Latencyofexit,s CLW LW CIT CLW LW CIT 0 50 100 150 Timespentinlitbox,s CLW LW CIT CLW LW CIT 0 5 10 15 WT HET * Numberofexits,n
- 19. Glucose tolerance Fasted 18 hours, 1.5 mg/g ip glucose
- 20. Summary 5 HTT +/- aged females show lower cognitive performance and increased symptoms of anxiety LW was more effective in WT SERT animals but had efficacy in both groups for anxiety LW shows promise for improved glucose utilization
- 21. Timantti AB Stockholm, Sweden Prof Dr Klaus-Peter Lesch Molecular Psychiatry, Laboratory of Translational Neuroscience Zentrum für Psychische Gesundheit (ZEP) Füchsleinstraße 15 97080 Würzburg Germany Dr Tatyana Strekalova Maastricht University Department of Psychiatry and Neuropsychology School for Mental Health and Neuroscience (MHeNS) 6200 MD Maastricht The Netherlands Dr Dinora Lopes and Prof Henrique Silveira Global Health and Tropical Medicine Instituto de Higiene e Medicina Tropical Universidade NOVA de Lisboa Dr Brandon Cline Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques, INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Faculté de Médecine, Strasbourg, France
Editor's Notes
- Affective disorders are a set of psychiatric diseases, also called mood disorders. The main types of affective disorders are depression, bipolar disorder, and anxiety disorder.
- Diabetes prevalence vs. deuterium content in tap water (D/H) Diabetes prevalences for every state across continental USA were obtained from Centers for Disease Control and Prevention. Prevalence of diabetes among US adults (18+) (Percentage), 2009. Suggested Citation: Division for Heart Disease and Stroke Prevention: Data Trends & Maps Web site. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention (CDC), National Center for Chronic Disease Prevention and Health Promotion, Atlanta, GA, 2010. Available at http://www.cdc.gov/dhdsp/ http://apps.nccd.cdc.gov/NCVDSS_DTM/DetailedData.aspx?State=United+States&Category=6&Indicator=38&stratification=Total Deuterium content in tap water for every state across continental USA were obtained from Strekalova et al, Behavioural Brain Res 2015, 277: 237-244 (Suppl data). There is a significant linear correlation between prevalence of diabetes among adults = 18 years old and deuterium level in tap water across continental USA (Pearson’s r=0.64, p<0.000005). There is difference in average diabetes prevalence between states having average deuterium in tap water less than 140 ppm and more than 150 ppm.
- latency 2 way ANOVA for interaction, geno and treatment Duration 2 way ANVOA only for geno LW treatment increase the latency in both groups, better for WT, WT are better than HET Only WT animals have more floating in third session, no effect of treatment
- 2 way ANVOA for geno and treatment WT animals explore more, LW increased exploration in both
- 2 way ANOVA only for geno WT animals explored more
- 2 way ANVOA no effect
- 2 way ANOVA no effect in all test
- The effects of chronic administration of deuterium depleted water (DDW) 91 ppm on glucose tolerance after a challenge with glucose solution, in SERT-wt aged female mice. *p<0.05. vs 140 ppm-treated mice. Data are presented as mean + SEM. The effects of chronic administration of DDW 91 ppm on glucose tolerance after a challenge with glucose solution, in SERT-het aged female mice vs 140 ppm-treated mice.. Data are presented as mean + SEM.