REELIN and schizophrenia: a disease at the interface of the genome and the epigenome.
REELIN and schizophrenia: a disease at the interface of the genome and the epigenome.
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DOI：
10.1124/mi.2.1.47
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发表时间：
2002-02-01
影响因子：
--
通讯作者：
Guidotti, A
中科院分区：
文献类型：
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作者：
Costa, E;Chen, Y;Guidotti, A
在精神分裂症患者大脑中出现的瑞林基因（RELN）下调，其特征是锥体神经元树突缩短以及树突棘表达密度降低，这很可能是由RELN启动子的过度甲基化导致的。在成年哺乳动物大脑中，分泌γ - 氨基丁酸（GABA能）的中间神经元将RELN释放到细胞外基质中，在那里它与树突棘突触后密度处存在的整合素受体高亲和力结合，并且可能如本文所阐述的那样，在突触可塑性中发挥作用。在RELN单倍体不足的杂合型瑞特小鼠中，组蛋白去乙酰化酶抑制剂可增加DNA去甲基化酶活性并恢复RELN的表达。因此，这类抑制剂可能在降低高危个体患精神分裂症的易感性方面具有治疗价值。
The downregulation of the Reelin gene (RELN) that occurs in schizophrenic brains, which are characterized by pyramidal neurons with shortened dendrites and by reduced expression densities of dendritic spines, may well result from hypermethylation of the RELN promoter. In the adult mammalian brain, gamma-aminoburytic acid-secreting (GABAergic) interneurons release RELN into the extracellular matrix, where it binds with high affinity to the integrin receptors present at dendritic spine postsynaptic densities and likely plays a role, elaborated in this article, in synaptic plasticity. In heterozygous reeler mice, which are haploinsufficient in RELN, inhibitors of histone deacetylase increase DNA demethylase activity and restore RELN expression. Such inhibitors could thus be of therapeutic value in mitigating vulnerability to schizophrenia among high-risk individuals.