Positive and negative symptoms in schizophrenia: the NMDA receptor hypofunction hypothesis, neuregulin/ErbB4 and synapse regression
Positive and negative symptoms in schizophrenia: the NMDA receptor hypofunction hypothesis, neuregulin/ErbB4 and synapse regression
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DOI：
10.1080/00048670903001943
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发表时间：
2009-01-01
影响因子：
4.6
通讯作者：
Bennett, Maxwell
中科院分区：
文献类型：
--
作者：
Bennett, Maxwell
Carlsson提出了一种假说，即精神分裂症的阳性和阴性症状是由于谷氨酸N-甲基-d-天冬氨酸(NMDA)受体功能低下导致中脑边缘和中皮质投射失败所致。这本杂志最近强调了这一假设，即压力可能会导致NMDA受体突触棘突的丢失，这可以解释幻觉等阳性症状的出现，这种突触回归涉及到与精神分裂症有关的分子，如NeuRegin及其受体ErbB4。在这篇文章中，这两个假说被结合在一个单一的方案中，其中重点放在从neuRegin/ErbB4到NMDA受体的调制的分子通路，以及随后突触脊椎细胞骨架装置的变化，从而使脊椎退化。有人认为，鉴定这一途径的分子组成将允许合成合适的物质来消除NMDA受体的功能低下，从而消除这种功能低下所产生的表型后果。
Carlsson has put forward the hypothesis that the positive and negative symptoms of schizophrenia are due to failure of mesolimbic and mesocortical projections consequent on hypofunction of the glutamate N-methyl-d-aspartate (NMDA) receptor. The hypothesis has been recently emphasized in this Journal that the loss of synaptic spines with NMDA receptors, which can be precipitated by stress, can explain the emergence of positive symptoms such as hallucinations and that this synapse regression involves molecules such as neuregulin and its receptor ErbB4 that have been implicated in schizophrenia. In this essay these two hypotheses are brought together in a single scheme in which emphasis is placed on the molecular pathways from neuregulin/ErbB4, to modulation of the NMDA receptors, subsequent changes in the synaptic spine's cytoskeletal apparatus and so regression of the spines. It is suggested that identification of the molecular constituents of this pathway will allow synthesis of suitable substances for removing the hypofunction of NMDA receptors and so the phenotypic consequences that flow from this hypofunction.