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

Autor: Zhihong Yang, Yongzhen Miao, Chuanxia Ju, Lei Wang, Naidong Wang, Ruoyu Zhang, Zihan Xu, Wenjin Shao, Fang Zhang
Rok vydání: 2019
Předmět:
0301 basic medicine
medicine.medical_specialty
Genetic Vectors
Immunology
Neuroscience (miscellaneous)
Hippocampus
Mice
Transgenic
Adaptive Immunity
Biology
Injections
Proinflammatory cytokine
Pathogenesis
Amyloid beta-Protein Precursor
Mice
03 medical and health sciences
0302 clinical medicine
Alzheimer Disease
Internal medicine
mental disorders
Presenilin-1
medicine
Animals
Immunology and Allergy
Fear conditioning
Maze Learning
Neuroinflammation
Pharmacology
Memory Disorders
Intracellular Signaling Peptides and Proteins
Wild type
Gene Expression Regulation
Developmental
Fear
Genetic Therapy
Dependovirus
Acquired immune system
Immunity
Innate
Recombinant Proteins
Up-Regulation
Mice
Inbred C57BL
Disease Models
Animal
030104 developmental biology
Endocrinology
Cytokines
Tumor necrosis factor alpha
Cognition Disorders
030217 neurology & neurosurgery
Zdroj: Journal of Neuroimmune Pharmacology. 14:519-529
ISSN: 1557-1904
1557-1890
Popis: Neuroinflammation plays an early and prominent role in the pathology of Alzheimer's disease (AD). Tumor necrosis factor-α-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 between the APP/PS1 mice and the age-matched wild type (WT) mice at different stages of development using western blot and RT-qPCR. The hippocampal expression of the TIPE2 mRNA and protein in APP/PS1 mice was 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 the 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 APP/PS1 mice resulted in an improvement of learning and memory and reduced expression of inflammatory cytokines, such as TNF-α, IL-6 and IL-1β, and increased expression of anti-inflammatory cytokines, such as IL-10 and Arg-1. Taken together, our findings show that the TIPE2 expression level was negatively correlated with the pathogenesis of Alzheimer's disease, and overexpression of TIPE2 attenuates cognitive deficits in APP/PS1 mice, suggesting TIPE2 is a potential target for pharmacological intervention and improvement of cognitive deficits. Graphical Abstract .
Databáze: OpenAIRE
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