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. 2006 Feb;6(4):1230-6.
doi: 10.1002/pmic.200500412.

Alteration of the glutamate and GABA transporters in the hippocampus of the Niemann-Pick disease, type C mouse using proteomic analysis

Kyunghee Byun  1 , Jaewoo Kim, Sang-Yun Cho, Brian Hutchinson, Se-Ran Yang, Kyung-Sun Kang, Moonjae Cho, Kyukye Hwang, Makoto Michikawa, Young-Wook Jeon, Young-Ki Paik, Bonghee Lee
Affiliations

Alteration of the glutamate and GABA transporters in the hippocampus of the Niemann-Pick disease, type C mouse using proteomic analysis

Kyunghee Byun et al. Proteomics. 2006 Feb.

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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