Disc1 variation leads to specific alterations in adult neurogenesis.

Disc1 variation leads to specific alterations in adult neurogenesis.
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DOI:
10.1371/journal.pone.0108088
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Ffrench-Constant C
Ffrench-Constant C
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chandran JS;Kazanis I;Clapcote SJ;Ogawa F;Millar JK;Porteous DJ;Ffrench-Constant C

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精神分裂症1(DISC1)是一系列神经精神疾病的危险因素,包括精神分裂症,双相情感障碍和重度抑郁症。在这里,我们使用两个错义Disc1小鼠突变体,先前描述的不同的行为表型,以证明Disc1变异对成年海马中新生成的神经元的形成产生不同的影响。携带纯合Q31L突变并显示抑郁样表型的Disc1小鼠具有较少的增殖细胞,而具有诱导精神分裂症样表型的纯合L100P突变的Disc1小鼠显示海马齿状回中新产生的神经元的产生、放置和成熟的变化。我们的研究结果表明Disc1等位基因在成年海马体中的特异性作用,并表明行为表型的分歧可能部分源于大脑中特定细胞群的变化。
Disrupted in schizophrenia 1 (DISC1) is a risk factor for a spectrum of neuropsychiatric illnesses including schizophrenia, bipolar disorder, and major depressive disorder. Here we use two missense Disc1 mouse mutants, described previously with distinct behavioural phenotypes, to demonstrate that Disc1 variation exerts differing effects on the formation of newly generated neurons in the adult hippocampus. Disc1 mice carrying a homozygous Q31L mutation, and displaying depressive-like phenotypes, have fewer proliferating cells while Disc1 mice with a homozygous L100P mutation that induces schizophrenia-like phenotypes, show changes in the generation, placement and maturation of newly generated neurons in the hippocampal dentate gyrus. Our results demonstrate Disc1 allele specific effects in the adult hippocampus, and suggest that the divergence in behavioural phenotypes may in part stem from changes in specific cell populations in the brain.
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