遺傳學(xué)

來源出版物：Journal of Genetics and Genomics，2015，42（1）： 1-8聯(lián)系郵箱：Wei Li，wli@genetics.ac.cn

封面介紹：The gene，DTNBP1，which cncodes dysbindin-1，is known to be a susceptibility gene for schizophrenia. There exist three isoforms of dysbindin-1（1A IB and 1C）. In mouse，dysbindin-1 C，not 1A，is expressed in the hilar mossy cells of the dentate gyrus and is required for the survival of these neurogenesis. In this issue，Dr. Wei Li's group characterized that loss of dysbindin-1 C led to mossy cell loss via impaired basal autophagy. These findings support that schizophrenia could result from "eurodegeneration，and provide the link between autophagy and schizophrenia（Yuan et al.，pp. 1-8）.

Impaired Autophagy in Hilar Mossy Cells of the Dentate Gyrus and Its Implication in Schizophrenia

Yefeng Yuan，Hao Wang，Zongbo Wei，et al.

Schizophrenia（SCZ）is a complex disease that has been regarded as a neurodevelopmental，synaptic or epigenetic disorder. Here we provide evidence that neurodegeneration is implicated in SCZ. The DTNBP1（dystrobrevin-binding protein 1）gene encodes dysbindin-1 and is a leading susceptibility gene of SCZ. We previously reported that the dysbindin-1C isoform regulates the survival of the hilar glutamatergic mossy cells in the dentate gyrus，which controls the adult hippocampal neurogenesis. However，the underlying mechanism of hilar mossy cell loss in the dysbindin-1-deficient sandy（sdy）mice（a mouse model of SCZ）is unknown. In this study，we did not observe the apoptotic signals in the hilar mossy cells of the sdy mice by using the TUNEL assay and immunostaining of cleaved caspase-3 or necdin，a dysbindin-1- and p53-interacting protein required for neuronal survival. However，we found that the steady-state level of LC3-II，a marker of autophagosomes，was decreased in the hippocampal formation in the mice lacking dysbindin-1C. Furthermore，we observed a significant reduction of the cytosolic LC3-II puncta in the mossy cells of sdy mice. In addition，overexpression of dysbindin-1C，but not 1A，in cultured cells increased LC3-II level and the LC3 puncta in the transfected cells. These results suggest that dysbindin-1C deficiency causes impaired autophagy，which is likely implicated in the pathogenesis of SCZ.

Dysbindin-1； Mossy cell； Neurodegeneration； Autophagy； Schizophrenia