The effects of P2X7 receptor knockout on emotional conditions over the lifespan of mice.

Neuroinflammation is one of the key factors contributing to depression. Recent studies have identified P2X7 receptor (P2X7r) as a major inflammatory regulator. However, the effects of P2X7r knockout (KO) on emotional conditions over the lifespan of mice are unknown. In this study, the effects of P2X7r deletion on emotional conditions over the lifespan of mice were investigated in young-aged (2 month old), middle-aged (10 month old), and old-aged (18 month old) female P2X7r KO mice and age-matched female C57BL/6 mice. Behavioral tasks were conducted by open field test, forced swimming test and sucrose preference test. Mitochondrial structures and spine synapses in hippocampus were examined by electron microscopy. Enzyme-linked immunosorbent assay was used to analyze the expression of interleukin-1β and tumor necrosis factor-α. Western blot analysis was used to assess the expression of nuclear factor-kappa B (NF-κB) pathway-related proteins. The results indicated that middle-aged P2X7r KO mice displayed better emotional conditions than middle-aged WT mice. However, worse emotional conditions were observed in young-aged P2X7r KO mice. Moreover, abnormal mitochondrial structures and less spine synapses were observed in young-aged P2X7r KO mice. Mitochondrial structures were recovered and more spine synapses occurred in middle-aged P2X7r KO mice. In addition, expressions of interleukin-1β, tumor necrosis factor-α, p-IKKα, p-IKKβ, p-IκBα, and p-NF-κBp65 were decreased in middle-aged P2X7r KO mice, but increased in young-aged P2X7r KO mice. In conclusion, P2X7r KO improves the emotional conditions at later stages of the lifespan of mice, but not in all ages, suggesting time-specific roles of immune response in nervous system through NF-κB signaling pathway. Video abstract: http://links.lww.com/WNR/A494.