Overexpression of TIPE2, a Negative Regulator of Innate and Adaptive Immunity, Attenuates Cognitive Deficits in APP/PS1 Mice

Abstract

Neuroinflammation plays an early and prominent role in the pathology of Alzheimer's disease (AD). Tumor necrosis factor‐a‐induced protein 8‐like 2 (TIPE2) has been identified as a negative regulator of innate and adaptive immunity. However, whether TIPE2 affects cognitive functions in AD‐like mouse models remains unknown. In this study, we compared the gene and protein expressions of TIPE2 and β‐amyloid in the brain between the APP/PS1 mice and the age‐matched wild type (WT) mice at different stages of developments using assays of immunofluorescence, western blot and qPCR. Deposition of Aβ plaques appeared in the hippocampus from the 6‐month‐old APP/PS1 mice, and the hippocampal expression of the TIPE2 mRNA and protein in APP/PS1 mice were significantly higher than that of the WT mice starting from 6 months to 10 months. However, the difference of the TIPE2 expression between the APP/PS1 mice and the WT mice declined in a time‐dependent manner. The spatial learning and memory deficit from 8‐month‐old APP/PS1 mice was observed in the Y‐maze test and fear conditioning task. Interestingly, overexpression of TIPE2 by intra‐hippocampal injection of AAV‐TIPE2 into the 7‐month old APP/PS1 mice resulted in an improvement of learning and memory. Taken together, our findings show that the TIPE2 expression level was negatively correlated with the Alzheimer's disease, suggesting TIPE2 is a potential target for pharmacological intervention and improvement of cognitive deficits.Support or Funding InformationThis work was supported by research grants to Fang ZHANG from the Natural Science Foundation of Shandong Province of China, No. ZR2016 HM 46; Post doctoral application foundation of Qingdao Municipal Bureau of Social Sciences, No. 2016062; Qingdao science and technology bureau, No 18‐6‐1‐75‐nsh; Clinical medicine +X Project of Qingdao University Medical Department; Innovation and Entrepreneurship Training Program of undergraduate student in Qingdao University. No. 201711065152.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.