title: Changes of gene expression of Gal3, Hsp27, Lcn2, and Timp1 in rat substantia nigra following medial forebrain bundle transection using a candidate gene microarray.
abstract: Neuroinflammation is an early event and important contributor to the pathobiology of neurodegenerative diseases. Neuroglia, especially microglia, are a major central nervous system population that can modulate neuroinflammation. To determine potential key molecules in this process, we employed microarray analysis in the substantia nigra (SN) following medial forebrain bundle (MFB) transection and analyzed the temporal expression profiles of candidate genes implicated in neuroglial activation and functional maturation. The DNA microarray analyzed, 8913 probes. Sixty nine genes were up-regulated and 11 genes were down-regulated at least twofold compared to normal control. Of the 80 genes, 23 were related to cell metabolism, 3 related to apoptosis, 27 related to immunity. Among them, 4 genes (Galectin 3, Heat shock protein 27, Lipocalin 2, Tissue inhibitory metalloproteinase 1) seemed to be related to the neuroglial function. The candidate genes were subjected to quantitative real-time PCR, Western blotting, and immunohistochemical approaches. Expression changes similar to the microarray were evident. In a double immunofluorescence assay, Galectin 3 almost completely co-localized with OX6-positive activated microglia, and Heat shock protein 27 mainly co-localized with glial fibrillary acidic protein (GFAP) positive astrocytes. Lipocalin 2, except for a few matches of GFAP positive astrocytes, did not co-localized with any of neuroglial markers. This is the first study to evaluate gene expression changes in the SN following MFB transection, which has been used as a parkinsonian animal model. Several candidate genes with potential roles in neuroglial activation and functional maturation were identified. The molecular significance of the candidate genes in neuroglial activation and neuroinflammation remains unclear.
authors: Department of Anatomy and Neuroscience, Eulji University School of Medicine, Daejeon, Republic of Korea; Department of Ophthalmology, Eulji University Hospital, Daejeon, Republic of Korea.
authors: Yoon-Jung
authors: YJ
authors: Choy
authors: Department of Anatomy and Neuroscience, Eulji University School of Medicine, Daejeon, Republic of Korea.
authors: Sung-Young
authors: SY
authors: Hong
authors: Department of Anatomy and Neuroscience, Eulji University School of Medicine, Daejeon, Republic of Korea.
authors: Sang-Jin
authors: SJ
authors: Pack
authors: Department of Anatomy and Neuroscience, Eulji University School of Medicine, Daejeon, Republic of Korea.
authors: Ran-Sook
authors: RS
authors: Woo
authors: Department of Anatomy and Neuroscience, Eulji University School of Medicine, Daejeon, Republic of Korea.
authors: Tai-Kyoung
authors: TK
authors: Baik
authors: Department of Anatomy and Neuroscience, Eulji University School of Medicine, Daejeon, Republic of Korea. Electronic address: dysong@eulji.ac.kr.
authors: Dae-Yong
authors: DY
authors: Song
mesh_terms: D000818:Animals; D019771:Axotomy; D015153:Blotting, Western; D037502:Galectin 3 / Q000096:biosynthesis*; D055551:HSP27 Heat-Shock Proteins / Q000096:biosynthesis; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism; D000071068:Lipocalin-2; D054834:Lipocalins / Q000096:biosynthesis*; D008297:Male; D008474:Medial Forebrain Bundle / Q000293:injuries*; D017628:Microglia / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D013378:Substantia Nigra / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis*; D059467:Transcriptome
chemical_list: D037502:Galectin 3; D055551:HSP27 Heat-Shock Proteins; C097278:Lcn2 protein, rat; D000071068:Lipocalin-2; D054834:Lipocalins; D019715:Tissue Inhibitor of Metalloproteinase-1
keywords: DNA microarray; Galectin 3; Heat shock protein 27; Lipocalin 2; Tissue inhibitory metalloproteinase 1