Damage of striatal neurons mediated by NMDA receptors in glutaric aciduria type Ⅰ / 临床儿科杂志

ABSTRACT

Objective To explore the excitotoxic role of NMDA receptors in striatal neurons in glutaric aciduria type I (GA1). Methods A GA1 cell model was established by lentivirus-mediated shRNA to GCDH and excessive intake of lysine. The expression levels of NMDA receptors were determined by Western blotting. The striatal neurons were preprocessed by MK801(a NMDA receptor antagonist), then infected with lentivirus and cultured in high concentration lysine. Cell viability was measured using MTT. Apoptosis was assessed using Hoechst33342 staining. Results Compared with the control group, the expression of NR2B protein in the experimental group was increased, and there was statistical difference (P<0.001). The differentces in the cell viability and normal nuclear proportion among experimental group, control group, and MK-801 pretreatment group were statistically significant (P<0.01). The cell viability and normal nucleus proportion in experimental group were significantly lower than those in control group while they were significantly higher in MK-801 pretreated group than those in the experiment group but still significantly lower than those in control group (P all <0.05). Conclusion The accumulation of metabolites in GA 1 played a toxic role in striatal neurons through NMDR receptors.