ABSTRACT
Objective:To investigate the effect and mechanisms of lateral ventricular injection of interferon-alpha (IFN-α) on electrophysiological activity in central nervous system.Methods:Twenty male Kunming mice were selected and subjected to auditory cortical electrode implantation and lateral ventricle intubation under general anesthesia. After one week of recovery, all mice were randomly divided into IFN-α group ( n=10) and normal saline group ( n=10). IFN-α and saline were administered by lateral ventricle injection for 7 consecutive days, and the auditory steady-state response(ASSR) in auditory cortex were recorded. Then the brain tissue was perfused, and the changes of microglia and astrocytes in the hippocampus were observed by immunohistochemical staining. Results:There was no significant difference in the average intensity of ASSR between the saline group and the IFN-α group((3.22±0.87)dB vs (3.49±0.56)dB; t=0.84, P=0.41) before administration.After administration, the average intensity of ASSR in IFN-α group was significantly lower than that before administration ((3.22±0.87)dB vs (1.59±0.44)dB, t=5.27, P<0.01), while the ASSR in saline group did not change before and after administration((3.49±0.56)dB, (3.46±0.61)dB; t=0.12, P=0.90). Immunohistochemistry revealed that the number of astrocytes and microglia in hippocampal CA1, CA3, and DG regions in the IFN-α group was higher than that of the saline group. Obvious morphological changes were also observed in the astrocytes and microglia. Conclusion:IFN-α can induce the activation of glial cells in the hippocampus and lead to the abnormal electrophysiological activity in the cortex. ASSR can reflect IFN-α induced brain dysfunction, which may be a potential indicator for early diagnosis.