Chronic administration of cyclosporine A changes expression of BDNF and TrkB in rat hippocampus and midbrain.
Neurotrophins, including the brain-derived neurotrophic factor (BDNF), are essential for regulating neuronal differentiation in developing brains. BDNF and its receptor tyrosine kinase receptor B (TrkB) are involved in neuronal signaling, survival and plasticity. Cyclosporine A (CsA) is a potent immunosuppressive agent which prevents allograft rejection in organ transplantation and various immunological diseases. We investigated whether chronic administration of CsA decreases BDNF gene expression in rats, and the influence of CsA on mRNA levels of TrkB receptors was also examined. For 30 days of CsA (10 mg/kg/day) administration, the expression of BDNF and TrkB mRNA was significantly decreased in the hippocampus and midbrain, but there was no significant difference in the cortex. CsA (0, 1, 5 10, 15 ug/ml) down-regulated BDNF and TrkB gene expression through cultured SH-SY5Y cells, as did all-trans retinoic acid (ATRA), and there was no effect on cell viability. These experimental results indicate that suppression of the BDNF and TrkB mRNA, protein level of BDNF expression in the hippocampus and midbrain may be related to altered behavior observed following chronic administration of CsA. A common mechanism of adverse effects of CsA induced depressive symptoms may involve neurotoxicity mediated by down-regulation of brain BDNF and TrkB.
Chen
Chien-Chih
CC
Department of Psychiatry, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, 123 Ta-Pei Rd, Niao-Sung, Kaohsiung, 83305, Taiwan, ROC.
Hsu
Li-Wen
LW
Huang
Li-Tung
LT
Huang
Tiao-Lai
TL
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D016572:Cyclosporine / Q000009:adverse effects*; D015536:Down-Regulation; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D008636:Mesencephalon / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020813:Receptor, trkB / Q000096:biosynthesis* / Q000235:genetics
D019208:Brain-Derived Neurotrophic Factor; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D016572:Cyclosporine; D020813:Receptor, trkB