Influence of Tacrolimus on Depressive-Like Behavior in Diabetic Rats Through Brain-Derived Neurotrophic Factor Regulation in the Hippocampus.

Neurotox Res

Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, The Catholic University of Korea, School of Medicine, 222 Banpo-daero, Seocho-gu, Seoul, 06501, Republic of Korea.

Published: August 2019

The neurotoxicity of immunosuppressive agents and diabetes mellitus are known risk factors of neurological complications in kidney transplant recipients. The aim of the present study was to investigate the influence of tacrolimus on brain-derived neurotrophic factor (BDNF), the critical protein for maintenance of neuronal functions, in the hippocampus in a diabetic condition. A diabetic rat model was established by a single streptozotocin injection (60 mg/kg). Control and diabetic rats then received daily tacrolimus (1.5 mg/kg per day) injections for 6 weeks. BDNF expression in the hippocampus was examined in the dentate gyrus (DG) and CA3 region using immunohistochemistry. There was a significant decrease of BDNF expression in the DG and CA3 region in tacrolimus-treated and diabetic rats compared with that of the control group injected with vehicle only. However, there was no difference in BDNF expression between the two experimental groups. Tacrolimus treatment in diabetic rats further decreased the BDNF expression level in the DG and CA3 region. Interestingly, mossy fiber sprouting, demonstrated by prominent punctate immunolabeling of BDNF with synaptoporin, was observed in the diabetic group treated with tacrolimus, which localized at the stratum oriens of the CA3 region. These data suggest that tacrolimus treatment or a diabetic condition decreases BDNF expression in the hippocampus, and that tacrolimus treatment in the diabetic condition further injures the CA3 region of the hippocampus. In addition to BDNF expression, decreased locomotor activity and evident depressive behavior were observed in tacrolimus-treated diabetic rats. Moreover, there were significant decreases of the mRNA levels of γ-aminobutyric acid and serotonin receptors in the diabetic hippocampus with tacrolimus treatment. This finding suggests that tacrolimus treatment may cause further psychiatric and neurological complications for patients with diabetes, and should thus be used with caution.

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12640-019-00062-6DOI Listing

Publication Analysis

Top Keywords

bdnf expression
24
diabetic rats
20
ca3 region
20
tacrolimus treatment
20
diabetic condition
12
treatment diabetic
12
diabetic
11
influence tacrolimus
8
brain-derived neurotrophic
8
neurotrophic factor
8

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!