Guidotti A, Pesold C, Costa E
Psychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois at Chicago, 60612, USA.
Neurochem Res. 2000 Oct;25(9-10):1207-18. doi: 10.1023/a:1007635927069.
Reelin (Reln) is expressed in specific GABAergic neurons in layer I and II of neocortex, and is secreted into the extracellular matrix where it surrounds dendrites, spines and neurite arborizations, and binds to integrin receptors located on post-synaptic densities of apical dendritic spines. Experiments in rodents (including wild type or reeler heterozygous mice) and non-human primates suggest the Reln secreted in the extracellular matrix of neocortex, via integrin receptors, modulates the function of the adaptor protein DAB1(drosophila disable-gene) homologous product) thereby participating in dynamic processes associated with plasticity changes in dendrites, dendritic spines and their synapses. A local protein synthesis at dendritic spines (ie the activity regulated cytoskeleton associated protein, Arc) probably acts as a signal for plastic modulatory activities in synapses operative in neural group interactions. A research strategy directed toward identifying specific neurochemical markers operative in the etiopathology of psychotic disorders lead to the identification of a downregulation (30-50%) of Reln and glutamic acid decarboxylase 67(GAD67) expression in prefrontal cortex and other brain areas of schizoprenia and bipolar disorder patients with psychosis. These downregulations were not due to neuronal damage, postmortem interval, or antipsychotic medication. The dysfunction of GABAergic interneurons observed in psychotic brains in combination with reduced Reln expression and downregulation of Reln-integrin receptor interaction, may provide an explanation for the reported decrease in neuropile expression including dendritic spine density reduction, in neocortex of schizophrenia patients. This downregulation of neuropile plasticity may be a factor to be considered in the etiology of the disintegration of consciousness, which is one of the primary signs of psychosis.
Reelin（Reln）在新皮层I层和II层的特定γ-氨基丁酸能神经元中表达，并分泌到细胞外基质中，在那里它围绕着树突、棘突和神经突分支，并与位于顶端树突棘突触后密度上的整合素受体结合。在啮齿动物（包括野生型或Reeler杂合小鼠）和非人类灵长类动物身上进行的实验表明，新皮层细胞外基质中分泌的Reln通过整合素受体调节衔接蛋白DAB1（果蝇失活基因同源产物）的功能，从而参与与树突、树突棘及其突触可塑性变化相关的动态过程。树突棘处的局部蛋白质合成（即活性调节细胞骨架相关蛋白，Arc）可能作为突触中神经组相互作用中可塑性调节活动的信号。一项旨在识别精神障碍病因中起作用的特定神经化学标志物的研究策略，导致在精神分裂症和双相情感障碍伴精神病患者的前额叶皮层和其他脑区中发现Reln和谷氨酸脱羧酶67（GAD67）表达下调（30%-50%）。这些下调并非由于神经元损伤、死后间隔或抗精神病药物治疗。在精神病患者大脑中观察到的γ-氨基丁酸能中间神经元功能障碍，与Reln表达降低和Reln-整合素受体相互作用下调相结合，可能为精神分裂症患者新皮层中报道的神经毡表达减少（包括树突棘密度降低）提供一种解释。神经毡可塑性的这种下调可能是在精神病的主要症状之一意识解体的病因中需要考虑的一个因素。
