Effect of PI3K pathway on tight junction and brain dysfunction in anti-NMDAR encephalitis mice

Objective:To explore the molecular mechanism of brain injury in anti-N-methyl-D-aspartate recep-tor(NMDAR)encephalitis mice by detecting the effect of phosphoinositide 3 kinase(PI3K)on the expressions of tight junction (TJ) proteins Occludin, Claudin-5 and neuron-specific nuclear (NeuN) in anti-NMDAR encephali-tis mice.Methods:A mouse model of anti-NMDAR encephalitis was established by peptide active immunization method.The mice were randomly divided into control, model, model+8 mg/kg LY294002, and model+16 mg/kg LY294002 groups.Neurobehavioral deficit scores were performed in each group.The blood-brain barrier(BBB) permeability was measured by fluorescein sodium assay.Western blotting was used to detect the expres-sions of Occludin, Claudin-5, and NeuN.Real-time fluorescence quantitative polymerase chain reaction (RT-qP-CR)was used to test the mRNA levels of Occludin and Claudin-5.The expression of NeuN in the brain was ana-lyzed by immunohistochemistry.Results:Compared with the control group, the short-term and long-term neuro-logical function scores of the model group mice decreased, the expression levels of Occludin, Claudin-5, and NeuN significantly decreased (P< 0.05), while the permeability of BBB increased.PI3K inhibitor LY294002 im-proved the nerve function of mice with anti-NMDAR encephalitis and suppressed the decrease of Occludin, Clau-din-5, and NeuN expression levels (All P< 0.05).Conclusion:The destruction of BBB may be one of the underlying mechanisms of brain injury in anti-NMDAR encephalitis mice.PI3K inhibition may pro-tect BBB integrity by up-regulating the expressions of Occludin, Claudin-5, and NeuN, thereby improving neural behavior in mice with anti-NMDAR encephalitis.