title: BDNF regulates GLAST and glutamine synthetase in mouse retinal Müller cells.
abstract: This study investigated whether brain-derived neurotrophic factor (BDNF) regulates the L-glutamate/L-aspartate transporter (GLAST) and glutamine synthetase (GS) in mouse retinal Müller cells (RMCs) under normal and hypoxic conditions. Mouse RMCs were treated with recombinant human BDNF (50, 75, 100, 125, or 150  ng/ml) for 24  h or underwent hypoxia induced by CoCl(2) (125  µM; 6, 12, 24, 48, or 72  h). An additional group underwent combined treatment with BDNF (100  ng/ml; 24, 48, 72, or 96  h) and CoCl(2) (125  µM/ml; 72  h). GLAST and GS mRNA and protein expression, L-[3,4-3H]-glutamic acid uptake, and apoptosis were assessed. BDNF dose-dependently up-regulated GLAST and GS mRNA and protein and increased glutamate uptake. Similarly, in early-stage CoCl(2)-induced hypoxia, GLAST and GS were up-regulated and glutamate uptake increased, but these decreased over time. BDNF also up-regulated GLAST and GS and increased glutamate uptake when RMCs under CoCl(2) induced hypoxic condition. However, BDNF treatment 24  h before CoCl(2) had no effect on GLAST or GS expression. CoCl(2) alone or combined with BDNF did not induce apoptosis. Hypoxia rapidly increased GLAST and GS expressions. This effect was transient, perhaps due to compensatory mechanisms that reduce GLAST and GS by 72  h. BDNF can up-regulate GLAST and GS and increase glutamate uptake during hypoxia, and these functions may underlie its neuroprotective effects.
authors: Department of Ophthalmology, Xiangya Hospital of Central South University, Changsha 410006, China.
authors: Min
authors: M
authors: Dai
authors: Xiao-Bo
authors: XB
authors: Xia
authors: Si-Qi
authors: SQ
authors: Xiong
mesh_terms: D000818:Animals; D017302:Annexins; D017209:Apoptosis; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D003035:Cobalt / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D027341:Excitatory Amino Acid Transporter 1 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D005974:Glutamate-Ammonia Ligase / Q000235:genetics / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000139:chemically induced; D051379:Mice; D012160:Retina / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
chemical_list: D017302:Annexins; D019208:Brain-Derived Neurotrophic Factor; D027341:Excitatory Amino Acid Transporter 1; C493393:Slc1a3 protein, mouse; D003035:Cobalt; D018698:Glutamic Acid; D005974:Glutamate-Ammonia Ligase; C018021:cobaltous chloride