STUDY OBJECTIVE: Sleep and mood disorders have long been understood to have strong genetic components, and there is considerable comorbidity of sleep abnormalities and mood disorders, suggesting the involvement of common genetic pathways. Here, we examine a candidate gene implicated in the regulation of both sleep and affective behavior using a knockout mouse model. DESIGN: Previously, we identified a quantitative trait locus (QTL) for REM sleep amount, REM sleep bout number, and wake amount in a genetically segregating population of mice. Here, we show that traits mapping to this QTL correlated with an expression QTL for neurotensin receptor 1 (Ntsr1), a receptor for neurotensin, a ligand known to be involved in several psychiatric disorders. We examined sleep as well as behaviors indicative of anxiety and depression in the NTSR1 knockout mouse. MEASUREMENTS AND RESULTS: NTSR1 knockouts had a lower percentage of sleep time spent in REM sleep in the dark phase and a larger diurnal variation in REM sleep duration than wild types under baseline conditions. Following sleep deprivation, NTSR1 knockouts exhibited more wake and less NREM rebound sleep. NTSR1 knockouts also showed increased anxious and despair behaviors. CONCLUSIONS: Here we illustrate a link between expression of the Ntsr1 gene and sleep traits previously associated with a particular QTL. We also demonstrate a relationship between Ntsr1 and anxiety and despair behaviors. Given the considerable evidence that anxiety and depression are closely linked with abnormalities in sleep, the data presented here provide further evidence that neurotensin and Ntsr1 may be a component of a pathway involved in both sleep and mood disorders.
STUDY OBJECTIVE:Sleep and mood disorders have long been understood to have strong genetic components, and there is considerable comorbidity of sleep abnormalities and mood disorders, suggesting the involvement of common genetic pathways. Here, we examine a candidate gene implicated in the regulation of both sleep and affective behavior using a knockout mouse model. DESIGN: Previously, we identified a quantitative trait locus (QTL) for REM sleep amount, REM sleep bout number, and wake amount in a genetically segregating population of mice. Here, we show that traits mapping to this QTL correlated with an expression QTL for neurotensin receptor 1 (Ntsr1), a receptor for neurotensin, a ligand known to be involved in several psychiatric disorders. We examined sleep as well as behaviors indicative of anxiety and depression in the NTSR1 knockout mouse. MEASUREMENTS AND RESULTS:NTSR1 knockouts had a lower percentage of sleep time spent in REM sleep in the dark phase and a larger diurnal variation in REM sleep duration than wild types under baseline conditions. Following sleep deprivation, NTSR1 knockouts exhibited more wake and less NREM rebound sleep. NTSR1 knockouts also showed increased anxious and despair behaviors. CONCLUSIONS: Here we illustrate a link between expression of the Ntsr1 gene and sleep traits previously associated with a particular QTL. We also demonstrate a relationship between Ntsr1 and anxiety and despair behaviors. Given the considerable evidence that anxiety and depression are closely linked with abnormalities in sleep, the data presented here provide further evidence that neurotensin and Ntsr1 may be a component of a pathway involved in both sleep and mood disorders.
Authors: Joshua Millstein; Christopher J Winrow; Andrew Kasarskis; Joseph R Owens; Lili Zhou; Keith C Summa; Karrie Fitzpatrick; Bin Zhang; Martha H Vitaterna; Eric E Schadt; John J Renger; Fred W Turek Journal: Sleep Date: 2011-11-01 Impact factor: 5.849
Authors: Seth A Ament; Szabolcs Szelinger; Gustavo Glusman; Justin Ashworth; Liping Hou; Nirmala Akula; Tatyana Shekhtman; Judith A Badner; Mary E Brunkow; Denise E Mauldin; Anna-Barbara Stittrich; Katherine Rouleau; Sevilla D Detera-Wadleigh; John I Nurnberger; Howard J Edenberg; Elliot S Gershon; Nicholas Schork; Nathan D Price; Richard Gelinas; Leroy Hood; David Craig; Francis J McMahon; John R Kelsoe; Jared C Roach Journal: Proc Natl Acad Sci U S A Date: 2015-02-17 Impact factor: 11.205
Authors: Brian E Cade; Daniel J Gottlieb; Diane S Lauderdale; David A Bennett; Aron S Buchman; Sarah G Buxbaum; Philip L De Jager; Daniel S Evans; Tibor Fülöp; Sina A Gharib; W Craig Johnson; Hyun Kim; Emma K Larkin; Seung Ku Lee; Andrew S Lim; Naresh M Punjabi; Chol Shin; Katie L Stone; Gregory J Tranah; Jia Weng; Kristine Yaffe; Phyllis C Zee; Sanjay R Patel; Xiaofeng Zhu; Susan Redline; Richa Saxena Journal: Hum Mol Genet Date: 2015-10-13 Impact factor: 6.150
Authors: María Luisa Torruella-Suárez; Jessica R Vandenberg; Elizabeth S Cogan; Gregory J Tipton; Adonay Teklezghi; Kedar Dange; Gunjan K Patel; Jenna A McHenry; J Andrew Hardaway; Pranish A Kantak; Nicole A Crowley; Jeffrey F DiBerto; Sara P Faccidomo; Clyde W Hodge; Garret D Stuber; Zoé A McElligott Journal: J Neurosci Date: 2019-11-19 Impact factor: 6.167
Authors: Hillary L Woodworth; Bethany G Beekly; Hannah M Batchelor; Raluca Bugescu; Patricia Perez-Bonilla; Laura E Schroeder; Gina M Leinninger Journal: Cell Rep Date: 2017-12-12 Impact factor: 9.423
Authors: Chelsea A Vadnie; Jun Hyun Park; Noha Abdel Gawad; Ada Man Choi Ho; David J Hinton; Doo-Sup Choi Journal: Front Neurosci Date: 2014-09-18 Impact factor: 4.677