Ts1Cje Down syndrome model mice exhibit environmental stimuli-triggered locomotor hyperactivity and sociability concurrent with increased flux through central dopamine and serotonin metabolism.
Ts1Cje mice have a segmental trisomy of chromosome 16 that is orthologous to human chromosome 21 and display Down syndrome-like cognitive impairments. Despite the occurrence of affective and emotional impairments in patients with Down syndrome, these parameters are poorly documented in Down syndrome mouse models, including Ts1Cje mice. Here, we conducted comprehensive behavioral analyses, including anxiety-, sociability-, and depression-related tasks, and biochemical analyses of monoamines and their metabolites in Ts1Cje mice. Ts1Cje mice showed enhanced locomotor activity in novel environments and increased social contact with unfamiliar partners when compared with wild-type littermates, but a significantly lower activity in familiar environments. Ts1Cje mice also exhibited some signs of decreased depression like-behavior. Furthermore, Ts1Cje mice showed monoamine abnormalities, including increased extracellular dopamine and serotonin, and enhanced catabolism in the striatum and ventral forebrain. This study constitutes the first report of deviated monoamine metabolism that may help explain the basis for abnormal behaviors, including the environmental stimuli-triggered hyperactivity, increased sociability and decreased depression-like behavior in Ts1Cje mice.
Laboratory for Neurogenetics, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
Atsushi
A
Shimohata
Laboratory for Neurogenetics, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan; Department of Pathological Biochemistry, Division of Pathological Sciences, Kyoto Pharmaceutical University, Misasagi Nakauchi-cho 5, Yamashina-ku, Kyoto 607-8414, Japan.
Keiichi
K
Ishihara
Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
Satoko
S
Hattori
Laboratory for Neurogenetics, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
Hiroyuki
H
Miyamoto
Support Unit for Bio-Material Analysis, Research Resources Center, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
Hiromasa
H
Morishita
Molecular and Neuropathology Group, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
Guy
G
Ornthanalai
Laboratory for Neurogenetics, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
Matthieu
M
Raveau
Laboratory for Neurogenetics, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan; Department of Internal Medicine-Lymphoma Research Lab, Wayne State University & School of Medicine, Room#8229, Scott Hall, 540E Canfield, Detroit, MI 48201, USA.
Abdul Shukkur
AS
Ebrahim
Laboratory for Neurogenetics, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
Kenji
K
Amano
School of Management, Shizuoka Sangyo University, 1572-1, Owara, Iwata-shi, Shizuoka 438-0043, Japan.
Kazuyuki
K
Yamada
Center of Maternal-Fetal, Neonatal and Reproductive Medecine, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan.
Haruhiko
H
Sago
Department of Pathological Biochemistry, Division of Pathological Sciences, Kyoto Pharmaceutical University, Misasagi Nakauchi-cho 5, Yamashina-ku, Kyoto 607-8414, Japan.
Satoshi
S
Akiba
Support Unit for Bio-Material Analysis, Research Resources Center, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
Nobuko
N
Mataga
Molecular and Neuropathology Group, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
Niall P
NP
Murphy
Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan; Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, 38 Nishigo-naka, Okazaki, Aichi 444-8585, Japan.
Tsuyoshi
T
Miyakawa
Laboratory for Neurogenetics, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan. Electronic address: yamakawa@brain.riken.jp.
Kazuhiro
K
Yamakawa
D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D003072:Cognition Disorders / Q000209:etiology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D004314:Down Syndrome / Q000150:complications / Q000235:genetics / Q000473:pathology; D004777:Environment; D005106:Exploratory Behavior; D005260:Female; D006948:Hyperkinesis / Q000209:etiology* / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D050697:Retinal Dehydrogenase; D012701:Serotonin / Q000378:metabolism*; D014314:Trisomy / Q000235:genetics; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D012701:Serotonin; D014446:Tyrosine 3-Monooxygenase; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C515028:ALDH1A1 protein, mouse; D050697:Retinal Dehydrogenase; C000593198:COMT protein, mouse; D002394:Catechol O-Methyltransferase; D001142:Aromatic-L-Amino-Acid Decarboxylases; D004298:Dopamine
Animal model; Behavioral analysis; Catechol-O-methyltransferase; Dopamine; Down syndrome; Hyperactivity; Monoamine; Serotonin; Sociability