In this study, qRT-PCR and Western blotting have shown that shRNA of MSTRG.81401 can reduce the upregulated expression of P2X7 in the hippocampus of rats with comorbid DNP and MDD, pointing to the role of lncRNA MSTRG.81401 in the pathogenesis of these diabetic complications. Here, P2RX7 is linked to major depressive disorder.