Chronic Administration of Cyclosporine A Changes Expression of BDNF and TrkB in Rat Hippocampus and Midbrain
- 2 April 2010
- journal article
- Published by Springer Science and Business Media LLC in Neurochemical Research
- Vol. 35 (7), 1098-1104
- https://doi.org/10.1007/s11064-010-0160-0
Abstract
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.Keywords
This publication has 28 references indexed in Scilit:
- Chronic Administration of Mood Stabilizers Upregulates BDNF and Bcl-2 Expression Levels in Rat Frontal CortexNeurochemical Research, 2008
- Calcineurin activity is required for depolarization‐induced, CREB‐dependent gene transcription in cortical neuronsJournal of Neurochemistry, 2007
- Functional Repression of cAMP Response Element in 6-Hydroxydopamine-treated Neuronal CellsOnline Journal of Public Health Informatics, 2006
- Cyclosporine A (CsA) affects the pharmacodynamics and pharmacokinetics of the atypical antipsychotic amisulpride probably via inhibition of P-glycoprotein (P-gp)Journal of Neural Transmission, 2005
- Mice lacking brain-derived neurotrophic factor develop with sensory deficitsNature, 1994
- Targeted disruption of the trkB neurotrophin receptor gene results in nervous system lesions and neonatal deathCell, 1993
- CyclosporinDrugs, 1993
- Cyclosporin-associated akinetic mutism and extrapyramidal syndrome after liver transplantation.Journal of Neurology, Neurosurgery & Psychiatry, 1990
- Central Nervous System Toxicity after Liver TransplantationThe New England Journal of Medicine, 1987
- COMPLICATIONS OF CYCLOSPORINE-PREDNISONE IMMUNOSUPPRESSION IN 402 RENAL ALLOGRAFT RECIPIENTS EXCLUSIVELY FOLLOWED AT A SINGLE CENTER FOR FROM ONE TO FIVE YEARSTransplantation, 1987