Mice Expressing the A53T Mutant Form of Human Alpha-Synuclein Exhibit Hyperactivity and Reduced Anxiety-Like Behavior

被引:112
作者
Graham, Dianca R. [1 ]
Sidhu, Anita [1 ]
机构
[1] Georgetown Univ, Dept Biochem Mol & Cellular Biol, Washington, DC 20007 USA
基金
美国国家卫生研究院;
关键词
behavior; dopamine transporter; anxiety disorders; Parkinson's disease; PARKINSONS-DISEASE; DOPAMINE TRANSPORTER; ALZHEIMERS-DISEASE; NOREPINEPHRINE TRANSPORTER; BINDING; MODULATION; MUTATION; LACKING; SYSTEM; BRAIN;
D O I
10.1002/jnr.22331
中图分类号
Q189 [神经科学];
学科分类号
071006 [神经生物学];
摘要
Genetic mutations associated with alpha-synuclein (alpha-Syn) are implicated in the pathogenesis of Parkinson's disease (PD). PD is primarily a movement disorder, but patients are known to experience anxiety and other mood disorders. In this study, we examined the effect of the hA53T mutation during development by analyzing the protein expression of norepinephrine (NET), serotonin (SERT), and dopamine (DAT) transporters in addition to assessing locomotor and anxiety-like behavior. We observed significant decreases in DAT expression at 8 months in transgenic animals compared with normal and younger mice. We used the elevated plus maze, open-field test, and rotarod apparatus to evaluate wild-type and hA53T hemizygous mice at 2, 8, and 12 months of age. Our results showed that 12-month-old transgenic mice spend more time in the open arms and display a greater number of open entries of the elevated plus maze compared with wild-type controls and younger mice. Open-field test results showed that 12-month-old mice travel a greater distance overall and travel more in the inner zone than either wild-type or younger mice. Rotarod testing showed that 8- and 12-month-old transgenic mice perform better than either wild-type controls or younger mice. Overall, 8-12-month-old transgenic mice showed a trend toward reduced anxiety-like behavior and increased hyperactivity. These results indicate a possible role of the A53T alpha-Syn mutation in anxiety-like and hyperactive behaviors in a PD mouse model, suggesting that these behaviors might be comorbid with this disease. (C) 2010 Wiley-Liss, Inc.
引用
收藏
页码:1777 / 1783
页数:7
相关论文
共 38 条
[1]
Mice lacking α-synuclein display functional deficits in the nigrostriatal dopamine system [J].
Abeliovich, A ;
Schmitz, Y ;
Fariñas, I ;
Choi-Lundberg, D ;
Ho, WH ;
Castillo, PE ;
Shinsky, N ;
Verdugo, JMG ;
Armanini, M ;
Ryan, A ;
Hynes, M ;
Phillips, H ;
Sulzer, D ;
Rosenthal, A .
NEURON, 2000, 25 (01) :239-252
[2]
α-Synuclein-positive structures in cases with sporadic Alzheimer's disease:: morphology and its relationship to tau aggregation [J].
Arai, Y ;
Yamazaki, M ;
Mori, O ;
Muramatsu, H ;
Asano, G ;
Katayama, Y .
BRAIN RESEARCH, 2001, 888 (02) :287-296
[3]
Galanin receptor subtype 2 (GalR2) null mutant mice display an anxiogenic-like phenotype specific to the elevated plus-maze [J].
Bailey, Kathleen R. ;
Pavlova, Maria N. ;
Rohde, Alex D. ;
Hohmann, John G. ;
Crawley, Jacqueline N. .
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 2007, 86 (01) :8-20
[4]
Cabin DE, 2002, J NEUROSCI, V22, P8797
[5]
Stabilization of α-synuclein secondary structure upon binding to synthetic membranes [J].
Davidson, WS ;
Jonas, A ;
Clayton, DF ;
George, JM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (16) :9443-9449
[6]
Concurrence of α-synuclein and tau brain pathology in the Contursi kindred [J].
Duda, JE ;
Giasson, BI ;
Mahon, ME ;
Miller, DC ;
Golbe, LI ;
Lee, VMY ;
Trojanowski, JQ .
ACTA NEUROPATHOLOGICA, 2002, 104 (01) :7-11
[7]
Interface between tauopathies and synucleinopathies: A tale of two proteins [J].
Galpern, WR ;
Lang, AE .
ANNALS OF NEUROLOGY, 2006, 59 (03) :449-458
[8]
α-synuclein transgenic mice exhibit reduced anxiety-like behaviour [J].
George, Sonia ;
van den Buuse, Maarten ;
Mok, Su San ;
Masters, Colin L. ;
Li, Qiao-Xin ;
Culvenor, Janetta G. .
EXPERIMENTAL NEUROLOGY, 2008, 210 (02) :788-792
[9]
Neuronal α-synucleinopathy with severe movement disorder in mice expressing A53T human α-synuclein [J].
Giasson, BI ;
Duda, JE ;
Quinn, SM ;
Zhang, B ;
Trojanowski, JQ ;
Lee, VMY .
NEURON, 2002, 34 (04) :521-533
[10]
Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter [J].
Giros, B ;
Jaber, M ;
Jones, SR ;
Wightman, RM ;
Caron, MG .
NATURE, 1996, 379 (6566) :606-612