title: Alteration of the glutamate and GABA transporters in the hippocampus of the Niemann-Pick disease, type C mouse using proteomic analysis.
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.
authors.affiliation: Department of Anatomy and Neurobiology, College of Medicine, Institute of Medical Science, Cheju National University, Jeju City, Jeju, South Korea.
authors.forename: Kyunghee
authors.initials: K
authors.lastname: Byun
authors.forename: Jaewoo
authors.initials: J
authors.lastname: Kim
authors.forename: Sang-Yun
authors.initials: SY
authors.lastname: Cho
authors.forename: Brian
authors.initials: B
authors.lastname: Hutchinson
authors.forename: Se-Ran
authors.initials: SR
authors.lastname: Yang
authors.forename: Kyung-Sun
authors.initials: KS
authors.lastname: Kang
authors.forename: Moonjae
authors.initials: M
authors.lastname: Cho
authors.forename: Kyukye
authors.initials: K
authors.lastname: Hwang
authors.forename: Makoto
authors.initials: M
authors.lastname: Michikawa
authors.forename: Young-Wook
authors.initials: YW
authors.lastname: Jeon
authors.forename: Young-Ki
authors.initials: YK
authors.lastname: Paik
authors.forename: Bonghee
authors.initials: B
authors.lastname: Lee
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000378:metabolism*; D000818:Animals; D015180:Electrophoresis, Gel, Two-Dimensional; D050580:Excitatory Amino Acid Transporter 3 / Q000378:metabolism; D050485:GABA Plasma Membrane Transport Proteins / Q000378:metabolism*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009457:Neuroglia / Q000378:metabolism; D000077296:Niemann-Pick C1 Protein; D009542:Niemann-Pick Diseases / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000502:physiology; D020543:Proteome / Q000032:analysis*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D027322:Amino Acid Transport System X-AG; D050580:Excitatory Amino Acid Transporter 3; D050485:GABA Plasma Membrane Transport Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000077296:Niemann-Pick C1 Protein; C106831:Npc1 protein, mouse; D011506:Proteins; D020543:Proteome; C493399:Slc1a1 protein, mouse; D005968:Glutamate Decarboxylase