[Abnormal expression of insulin receptor induced by Aβ(1-42) in rat hippocampus neuron].

Objective: To detect the expression change of insulin receptor under the induction of Aβ(1-42) in rat hippocampus neuron and thus from the receptor level explore the disorder of central nervous insulin signaling and molecular mechanism of Alzheimer's disease.

Methods: Cultured primary hippocampus neuron was treated with different concentrations of Aβ(1-42). Apoptosis was detected by flow cytometry. And real-time quantitative PCR (polymerase chain reaction) and Western blot were used to detect the expression of insulin receptor.

Results: Primary cultured cells, mature at Day 7, were identified as hippocampal cells. After the treatment with different concentrations of Aβ(1-42) (0 - 150 µmol/L), the ≥ 30 µmol/L treatment groups had greater early apoptosis rates (32.4%, 36.1%, 51.0%, 53.6%) than that in the control group (13.4%) in a concentration-dependent fashion. The PCR results showed that the levels of insulin receptor gene were significantly higher in 30 (2.56 ± 0.19) and 60 µmol/L (3.44 ± 0.23) treatment groups than that the control group (regarded as 1) (P < 0.01) while the 100µmol/L group (0.74 ± 0.15) was significantly lower than the control group (P < 0.01). And the results of Western blot had the same trend with those of PCR. The 30 and 60 µmol/L protein level of the treatment groups were 1.27 ± 0.13, 1.82 ± 0.10 (P < 0.01) and 100µmol/L group was 0.82 ± 0.08 (P < 0.05).

Conclusions: Aβ(1-42) induces an altered expression of insulin receptors in rat hippocampus cells and results in its functional defects. It may cause insulin resistance in center nervous system.