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

Yefeng Yuan; Hao Wang; Zongbo Wei; Wei Li

doi:10.1016/j.jgg.2014.12.001

Volume 42 Issue 1

Jan. 2015

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

doi: 10.1016/j.jgg.2014.12.001

Yefeng Yuan^{a, b},
Hao Wang^a,
Zongbo Wei^{a, b},
Wei Li^{a, c}

a
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
b
University of Chinese Academy of Sciences, Beijing 100039, China
c
Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing 100053, China

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Corresponding author: E-mail address: wli@genetics.ac.cn (Wei Li)
Received Date: 2014-10-08
Accepted Date: 2014-12-12
Rev Recd Date: 2014-12-08

Available Online: 2014-12-23

Publish Date: 2015-01-20

Abstract

Abstract

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 ofsdy 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

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References(33)

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