PMID- 25365803 OWN - NLM STAT- MEDLINE DCOM- 20150724 LR - 20181113 IS - 2162-3279 (Electronic) IS - 2162-3279 (Print) VI - 4 IP - 6 DP - 2014 TI - Type 1 equilibrative nucleoside transporter regulates astrocyte-specific glial fibrillary acidic protein expression in the striatum. PG - 903-14 LID - 10.1002/brb3.283 [doi] AB - BACKGROUND: Adenosine signaling has been implicated in several neurological and psychiatric disorders. Previously, we found that astrocytic excitatory amino acid transporter 2 (EAAT2) and aquaporin 4 (AQP4) are downregulated in the striatum of mice lacking type 1 equilibrative nucleoside transporter (ENT1). METHODS: To further investigate the gene expression profile in the striatum, we preformed Illumina Mouse Whole Genome BeadChip microarray analysis of the caudate-putamen (CPu) and nucleus accumbens (NAc) in ENT1 null mice. Gene expression was validated by RT-PCR, Western blot, and immunofluorescence. Using transgenic mice expressing enhanced green fluorescence protein (EGFP) under the control of the glial fibrillary acidic protein (GFAP) promoter, we examined EGFP expression in an ENT1 null background. RESULTS: Glial fibrillary acidic protein was identified as a top candidate gene that was reduced in ENT1 null mice compared to wild-type littermates. Furthermore, EGFP expression was significantly reduced in GFAP-EGFP transgenic mice in an ENT1 null background in both the CPu and NAc. Finally, pharmacological inhibition or siRNA knockdown of ENT1 in cultured astrocytes also reduced GFAP mRNA levels. CONCLUSIONS: Overall, our findings demonstrate that ENT1 regulates GFAP expression and possibly astrocyte function. FAU - Hinton, David J AU - Hinton DJ AD - Department of Psychiatry and Psychology, Mayo Clinic, College of Medicine Rochester, Minnesota, 55905 ; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, College of Medicine Rochester, Minnesota, 55905 ; Neurobiology of Disease Program, Mayo Clinic, College of Medicine Rochester, Minnesota, 55905. FAU - Lee, Moonnoh R AU - Lee MR AD - Department of Biochemistry and Molecular Biology, Mayo Clinic, College of Medicine Rochester, Minnesota, 55905. FAU - Jang, Jin Sung AU - Jang JS AD - Division of Pulmonary and Critical Care Medicine, Mayo Clinic, College of Medicine Rochester, Minnesota, 55905. FAU - Choi, Doo-Sup AU - Choi DS AD - Department of Psychiatry and Psychology, Mayo Clinic, College of Medicine Rochester, Minnesota, 55905 ; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, College of Medicine Rochester, Minnesota, 55905 ; Neurobiology of Disease Program, Mayo Clinic, College of Medicine Rochester, Minnesota, 55905. LA - eng GR - R01 AA018779/AA/NIAAA NIH HHS/United States GR - UL1 TR000135/TR/NCATS NIH HHS/United States GR - AA018779/AA/NIAAA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20140919 PL - United States TA - Brain Behav JT - Brain and behavior JID - 101570837 RN - 0 (Equilibrative Nucleoside Transporter 1) RN - 0 (Glial Fibrillary Acidic Protein) RN - 0 (Nerve Tissue Proteins) RN - 0 (RNA, Messenger) RN - 0 (SLC29A1 protein, mouse) RN - 0 (enhanced green fluorescent protein) RN - 0 (glial fibrillary astrocytic protein, mouse) RN - 147336-22-9 (Green Fluorescent Proteins) SB - IM MH - Animals MH - Astrocytes/*metabolism MH - Blotting, Western MH - Cell Line MH - Corpus Striatum/*metabolism MH - Equilibrative Nucleoside Transporter 1/antagonists & inhibitors/genetics/*metabolism MH - Fluorescent Antibody Technique MH - Gene Expression Profiling MH - Glial Fibrillary Acidic Protein MH - Green Fluorescent Proteins/genetics/metabolism MH - Male MH - Mice, 129 Strain MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Mice, Transgenic MH - Microarray Analysis MH - Nerve Tissue Proteins/genetics/*metabolism MH - Promoter Regions, Genetic MH - RNA, Messenger/metabolism MH - Real-Time Polymerase Chain Reaction PMC - PMC4178301 OTO - NOTNLM OT - Adenosine transporter OT - ENT1 OT - GFAP OT - astrocyte OT - microarray EDAT- 2014/11/05 06:00 MHDA- 2015/07/25 06:00 PMCR- 2014/11/01 CRDT- 2014/11/04 06:00 PHST- 2014/02/05 00:00 [received] PHST- 2014/06/30 00:00 [revised] PHST- 2014/08/26 00:00 [accepted] PHST- 2014/11/04 06:00 [entrez] PHST- 2014/11/05 06:00 [pubmed] PHST- 2015/07/25 06:00 [medline] PHST- 2014/11/01 00:00 [pmc-release] AID - BRB3283 [pii] AID - 10.1002/brb3.283 [doi] PST - ppublish SO - Brain Behav. 2014;4(6):903-14. doi: 10.1002/brb3.283. Epub 2014 Sep 19.