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Neurobiology of learning and memory v.146, 2017년, pp.12 - 20   SCI SCIE SSCI
본 등재정보는 저널의 등재정보를 참고하여 보여주는 베타서비스로 정확한 논문의 등재여부는 등재기관에 확인하시기 바랍니다.

Intra-nasal dopamine alleviates cognitive deficits in tgDISC1 rats which overexpress the human DISC1 gene

Wang, An-Li (Center for Behavioral Neuroscience, Institute of Experimental Psychology, Heinrich Heine University Düsseldorf, Germany ) ; Fazari, Benedetta (Center for Behavioral Neuroscience, Institute of Experimental Psychology, Heinrich Heine University Düsseldorf, Germany ) ; Chao, Owen Y. (Center for Behavioral Neuroscience, Institute of Experimental Psychology, Heinrich Heine University Düsseldorf, Germany ) ; Nikolaus, Susanne (Clinic of Nuclear Medicine, University Hospital Düsseldorf, Düsseldorf, Germany ) ; Trossbach, Svenja V. (Department Neuropathology, Medical Faculty, Heinrich Heine University Düsseldorf, Germany ) ; Korth, Carsten (Department Neuropathology, Medical Faculty, Heinrich Heine University Düsseldorf, Germany ) ; Sialana, Fernando J. (Department of Pharmaceutical Chemistry, University of Vienna, 1090, Austria ) ; Lubec, Gert (Department of Pharmaceutical Chemistry, University of Vienna, 1090, Austria ) ; Huston, Joseph P. (Center for Behavioral Neuroscience, Institute of Experimental Psychology, Heinrich Heine University Düsseldorf, Germany ) ; Mattern, Claudia (M et P Pharma AG, 6376 Emmetten, Switzerland ) ; de Souza Silva, Maria Angelica (Cen ) ;
  • 초록  

    Abstract The Disrupted-in-Schizophrenia 1 (DISC1) gene has been associated with mental illnesses such as major depression and schizophrenia. The transgenic DISC1 (tgDISC1) rat, which overexpresses the human DISC1 gene, is known to exhibit deficient dopamine (DA) homeostasis. To ascertain whether the DISC1 gene also impacts cognitive functions, 14–15 months old male tgDISC1 rats and wild-type controls were subjected to the novel object preference (NOP) test and the object-based attention test (OBAT) in order to assess short-term memory (1 h), long-term memory (24 h), and attention. Results : The tgDISC1 group exhibited intact short-term memory, but deficient long-term-memory in the NOP test and deficient attention-related behavior in the OBAT. In a different group of tgDISC1 rats, 3 mg/kg intranasally applied dopamine (IN-DA) or its vehicle was applied prior to the NOP or the OBAT test. IN-DA reversed cognitive deficits in both the NOP and OBAT tests. In a further cohort of tgDISC1 rats, post-mortem levels of DA, noradrenaline, serotonin and acetylcholine were determined in a variety of brain regions. The tgDISC1 group had less DA in the neostriatum, hippocampus and amygdala, less acetylcholine in neostriatum, nucleus accumbens, hippocampus, and amygdala, more serotonin in the nucleus accumbens, and less serotonin and noradrenaline in the amygdala. Conclusions : Our findings show that DISC1 overexpression and misassembly is associated with deficits in long-term memory and attention-related behavior. Since behavioral impairments in tgDISC1 rats were reversed by IN-DA, DA deficiency may be a major cause for the behavioral deficits expressed in this model. Highlights Rats with overexpressed human DISC1 gene show object attention deficits. Rats with overexpressed human DISC1 gene show deficits in long-term object memory. Intranasal dopamine can recover these cognitive deficits. DISC1 overexpression causes changes in monoamines and acetylcholine systems.


  • 주제어

    Intranasal dopamine .   DISC1 .   Novel object exploration .   Memory .   Attention .   Animal model.  

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