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Alteration of the glutamate and GABA transporters in the hippocampus of the Niemann-Pick disease, type C mouse using proteomic analysis
Authors:Byun Kyunghee  Kim Jaewoo  Cho Sang-Yun  Hutchinson Brian  Yang Se-Ran  Kang Kyung-Sun  Cho Moonjae  Hwang Kyukye  Michikawa Makoto  Jeon Young-Wook  Paik Young-Ki  Lee Bonghee
Institution:Department of Anatomy and Neurobiology, College of Medicine, Institute of Medical Science, Cheju National University, Jeju City, Jeju, South Korea.
Abstract:Niemann-Pick disease type C (NPC) is a fatal autosomal recessive cholesterol disorder characterized by severe progressive neurodegeneration. To unveil the mechanism of neurodegeneration, proteomic and morphological approaches were applied to the hippocampus in NPC -/- mouse. Two-DE was utilized to resolve the hippocampal protein expression profiles of 4- and 8-week-old NPC +/+ and -/- mice. Differentially expressed protein spots were identified by MALDI-TOF MS and database searching. At 4 weeks of age, there was no significant difference in protein profiles between NPC +/+ and -/- mice. However, at the age of 8 weeks, NPC +/+ and -/- mice showed marked difference in protein expressions. Among these, glutamate receptor 2 precursor was identified. The immunohistochemical study on neurotransporters showed that glial GABA transporter (GAT-3) increased in both 4- and 8-week-old NPC -/- mouse and glutamic acid decarboxylase (GAD-6) increased in 8-week-old NPC -/- mouse. Glial glutamate transporter, excitatory amino acids carrier-1 (EAAC1), decreased in 8-week-old NPC -/- mouse. In conclusion, our data may provide insight into the understanding of the basic mechanism through perturbation of protein networks and neurotransporter systems in a single gene knockout model of NPC disease.
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