Dissociation of impulsivity and aggression in mice deficient for the ADHD risk gene Adgrl3: Evidence for dopamine transporter dysregulation
Mortimer N., Ganster T., O'Leary A., Popp S., Freudenberg F., Reif A., Soler A. M., Ribasés M., Ramos-Quiroga J. A., Lesh K. Yu., Rivero O.
Neuropharmacology
Vol.156, Num.107504
Опубликовано: 2019
Тип ресурса: Статья
DOI:10.1016/j.neuropharm.2019.02.039
Аннотация:
Adhesion G protein-coupled receptor L3 (ADGRL3, LPHN3) has putative roles in neuronal migration and synapse function. Various polymorphisms in ADGRL3 have been linked with an increased risk of attention deficit/hyperactivity disorder (ADHD). In this study, we examined the characteristics of Adgrl3-deficient mice in multiple behavioural domains related to ADHD: locomotive activity, impulsivity, gait, visuospatial and recognition memory, sociability, anxiety-like behaviour and aggression. Additionally, we investigated the effect of Adgrl3-depletion at the transcriptomic level by RNA-sequencing three ADHD-relevant brain regions: prefrontal cortex (PFC), hippocampus and striatum. Adgrl3 −/− mice show increased locomotive activity across all tests and subtle gait abnormalities. These mice also show impairments across spatial memory and learning domains, alongside increased levels of impulsivity and sociability with decreased aggression. However, these alterations were absent in Adgrl3 +/ −
Ключевые слова:
Adhesion G protein-coupled receptor L3 (ADGRL3); Attention-deficit/hyperactivity disorder (ADHD); Hippocampus; Latrophilin; Latrophilin 3 (LPHN3); Mouse model; Prefrontal cortex; Striatum
dopamine transporter; neurohormone; neuropeptide; dopamine transporter; G protein coupled receptor; LPHN3 protein, mouse; receptor; Adgrl3 gene; adult; aggression; amphetamine dependence; animal experiment; animal model; anxiety; Article; attention deficit disorder; brain region; cohort analysis; controlled study; corpus striatum; depth perception; dopaminergic nerve cell; female; gait; gene; gene expression; genetic analysis; genetic code; genetic risk; hippocampus; impulsiveness; learning; locomotion; male; memory; mouse; nonhuman; pathogenesis; phenotype; prefrontal cortex; priority journal; RNA sequence; Slc6a3 gene; social aspect; spatial memory; aggression; animal; animal behavior; attention deficit disorder; brain; C57BL mouse; disease model; genetics; impulsiveness; knockout mouse; metabolism; physiology; Aggression; Animals; Attention Deficit Disorder with Hyperactivity; Behavior, Animal; Brain; Disease Models, Animal; Dopamine Plasma Membrane Transport Proteins; Female; Gene
Язык текста: Английский
ISSN: 1873-7064
Mortimer N.
Ganster T.
O'Leary A.
Popp S.
Freudenberg F.
Reif A.
Soler A. M. Artigas M.
Ribasés M.
Ramos-Quiroga J. A.
Lesh K. Yu. Klaus-Peter Yulius 1957-
Rivero O.
Мортимер Н.
Ганстер Т.
О'Леарy А.
Попп С.
Фреуденберг Ф.
Реиф А.
Солер А. М. Артигас М.
Рибасéс М.
Рамос-Qуирога Й. А.
Леш К. Ю. Клаус-Петер Юлиус 1957-
Риверо О.
Dissociation of impulsivity and aggression in mice deficient for the ADHD risk gene Adgrl3: Evidence for dopamine transporter dysregulation
Текст визуальный непосредственный
Neuropharmacology
Elsevier Science Publisher B.V.
Vol.156 Num.107504
2019
Статья
Adhesion G protein-coupled receptor L3 (ADGRL3) Attention-deficit/hyperactivity disorder (ADHD) Hippocampus Latrophilin Latrophilin 3 (LPHN3) Mouse model Prefrontal cortex Striatum
dopamine transporter neurohormone neuropeptide dopamine transporter G protein coupled receptor LPHN3 protein, mouse receptor Adgrl3 gene adult aggression amphetamine dependence animal experiment animal model anxiety Article attention deficit disorder brain region cohort analysis controlled study corpus striatum depth perception dopaminergic nerve cell female gait gene gene expression genetic analysis genetic code genetic risk hippocampus impulsiveness learning locomotion male memory mouse nonhuman pathogenesis phenotype prefrontal cortex priority journal RNA sequence Slc6a3 gene social aspect spatial memory aggression animal animal behavior attention deficit disorder brain C57BL mouse disease model genetics impulsiveness knockout mouse metabolism physiology Aggression Animals Attention Deficit Disorder with Hyperactivity Behavior, Animal Brain Disease Models, Animal Dopamine Plasma Membrane Transport Proteins Female Gene
Adhesion G protein-coupled receptor L3 (ADGRL3, LPHN3) has putative roles in neuronal migration and synapse function. Various polymorphisms in ADGRL3 have been linked with an increased risk of attention deficit/hyperactivity disorder (ADHD). In this study, we examined the characteristics of Adgrl3-deficient mice in multiple behavioural domains related to ADHD: locomotive activity, impulsivity, gait, visuospatial and recognition memory, sociability, anxiety-like behaviour and aggression. Additionally, we investigated the effect of Adgrl3-depletion at the transcriptomic level by RNA-sequencing three ADHD-relevant brain regions: prefrontal cortex (PFC), hippocampus and striatum. Adgrl3 −/− mice show increased locomotive activity across all tests and subtle gait abnormalities. These mice also show impairments across spatial memory and learning domains, alongside increased levels of impulsivity and sociability with decreased aggression. However, these alterations were absent in Adgrl3 +/ −