کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2200524 1551299 2014 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Alterations of GABAergic and dopaminergic systems in mutant mice with disruption of exons 2 and 3 of the Disc1 gene
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Alterations of GABAergic and dopaminergic systems in mutant mice with disruption of exons 2 and 3 of the Disc1 gene
چکیده انگلیسی


• PV-positive interneurons were reduced in female Disc1Δ2–3/Δ2–3 mice.
• METH-induced DA release was potentiated in female Disc1Δ2–3/Δ2–3 mice.
• mRNA levels of DA D1 and D2 receptors were increased in female Disc1Δ2–3/Δ2–3 mice.
• GABAergic and DAergic systems may be altered in female Disc1Δ2–3/Δ2–3 mice.

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 DISC1 may induce low anxiety and/or high impulsivity in mice with disruption of exons 2 and 3 of the Disc1 gene (Disc1Δ2–3/Δ2–3). It remains unclear, however, if deficiency of DISC1 leads to specific alterations in distinct neuronal systems. In the present study, to understand the role of DISC1 in γ-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 GABAA, DA transporter (DAT) and DA receptors in wild-type (Disc1+/+) and Disc1Δ2–3/Δ2–3 mice. Female Disc1Δ2–3/Δ2–3 mice showed a significant reduction of PV-positive interneurons in the hippocampus, while no apparent changes were observed in mRNA expression levels of GABAA receptor subunits. METH-induced DA release was significantly potentiated in the nucleus accumbens (NAc) of female Disc1Δ2–3/Δ2–3 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 Disc1Δ2–3/Δ2–3 mice. Male Disc1Δ2–3/Δ2–3 mice showed no apparent differences in all experiments. DISC1 may play a critical role in gender-specific developmental alteration in GABAergic inhibitory interneurons and DAergic neurons.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurochemistry International - Volume 74, July 2014, Pages 74–83
نویسندگان
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