The cytotoxic effect of methylglyoxal on BDNF and TrkB expression in rat hippocampal neurons / 中华行为医学与脑科学杂志

ABSTRACT

Objective To investigate the mechanisms of methylglyoxal(MG)-induced injury of hippocam-pal neurons. Methods Primary cultured of hippocampal neurons from 1-day-old Sprague-Dawley rats were incuba-ted with MG for different time and dose period. Cells proliferation were assayed by methyl thiazolyl tetrazolium (MTT),and apoptosis was quantified by flow cytometer using annexin V-FITC and propidium iodide (PI) stai-ning. The protein and mRNA levels of brain-derived neurotrophie factor (BDNF) and tyrosine kinase B(TrkB) were assayed with Western Blotting and real-time PCR. Results Treatment with MG resulted in a concentration-dependent (r=0.946, P < 0.01) and time-dependent (r=0.993, P < 0.01) decreasing neurons viability. Com-pared with Oh group(1. 633±0. 153)%, 100 μM MG treatment for 2h,6h, 12h and 24h,the cellular apeptosis rate were significantly increased ((2. 833±0. 153)%, (3. 367±0. 153)%, (4. 433±0. 404)% and (8. 833± 0. 306)% respectivdy,all P<0.01). MG also increased the BDNF mRNA and protein expression after 12h treat-ment (P<0.05 or P<0.01),but decreased the TrkB mRNA and protein expression in the cells after 6h treatment (P<0.05 or P < 0.01). Conclusion MG has direct toxic effect on hippocampal neurons and can impaire the BD-NF-TrkB signal pathway by inhibiting the expression of TrkB,and increasing the apoptosis of hippocampal neurons.