期刊
NEUROCHEMISTRY INTERNATIONAL
卷 74, 期 -, 页码 74-83出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuint.2014.06.009
关键词
Disc1; Dopamine release; Methamphetamine; Parvalbumin-positive interneuron; Schizophrenia
资金
- JSPS KAKENHI from JST [243493]
- JSPS
- SRPBS from MEXT, CREST
- MEXT [24111518, 25116515, 25460093, 26670121, 26293053]
- MHLW [H25-Iyaku-Ippan-020]
- Intramural Research Grant for Neurological and Psychiatric Disorders of NCNP [24-12]
- SRF Grant for Biomedical Research
- Grants-in-Aid for Scientific Research [25460093, 25116515, 26293053, 25830051, 24111518, 26670121] Funding Source: KAKEN
Disrupted-in-schizophrenia-1 (DISC1) has been widely associated with several psychiatric disorders, including schizophrenia, mood disorders and autism. We previously reported that a deficiency of DISCI may induce low anxiety and/or high impulsivity in mice with disruption of exons 2 and 3 of the Disc) gene (Disc1(Delta 2-3/Delta 2-3)). It remains unclear, however, if deficiency of DISCI leads to specific alterations in distinct neuronal systems. In the present study, to understand the role of DISCI in gamma-aminobutyric acid (GABA) interneurons and mesocorticolimbic dopaminergic (DAergic) neurons, we investigated the number of parvalbumin (PV)-positive interneurons, methamphetamine (METH)-induced DA release and the expression levels of GABA(A), DA transporter (DAT) and DA receptors in wild-type (Disc1(+/+)) and Disc1(Delta 2-3/Delta 2-3) mice. Female Disc1(Delta 2-3/Delta 2-3) mice showed a significant reduction of PV-positive interneurons in the hippocampus, while no apparent changes were observed in mRNA expression levels of GABA(A) receptor subunits. METH-induced DA release was significantly potentiated in the nucleus accumbens (NAc) of female Disc1(Delta 2-3/Delta 2-3) mice, although there were no significant differences in the expression levels of DAT. Furthermore, the expression levels of DA receptor mRNA were upregulated in the NAc of female Disc1(Delta 2-3/Delta 2-3) mice. Male Disc1(Delta 2-3/Delta 2-3) mice showed no apparent differences in all experiments. DISCI may play a critical role in gender-specific developmental alteration in GABAergic inhibitory interneurons and DAergic neurons. (C) 2014 Elsevier Ltd. All rights reserved.
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