Tlr7 Deletion Selectively Ameliorates Spatial Learning but does not Influence beta Deposition and Inflammatory Response in an Alzheimers Disease Mouse ModelAuthor(s): Hsin-Yu Liu, Yun-Fen Hung, Hong-Ru Lin, Tzu-Li Yen, Yi-Ping Hsueh
Alzheimer’s disease (AD) is highly associated with inflammation. Toll-like receptors (TLR), the critical pattern recognition receptors, initiate innate immune responses in a variety of cells. A role for TLR7 in AD has been postulated through its recognition of a specific miRNA that is upregulated in AD patients. In this report, we directly investigate the role of TLR7 in AD using mouse genetic models.
5XFAD mice were used here as a mouse model for AD. Behavioral features, brain anatomy, amyloid beta (Aβ) deposition, microglial activation and inflammatory cytokine production of wild-type, 5XFAD, Tlr7–/Y, and Tlr7–/Y; 5XFAD mice were compared to evaluate the role of TLR7 in AD.
Open field and Barnes maze paradigms were used to assess the effect of Tlr7 knockout on behaviors of AD mice. Among the various behavioral features, the spatial learning performance in Barnes maze of 5XFAD mice was noticeably improved following Tlr7 knockout. Using immunostaining and quantitative real time-PCR (Q-PCR), our data indicated that the hallmark of AD brains-including Aβ deposition, activation of microglial cells and astrocytes, and upregulation of inflammatory cytokines-are not altered by Tlr7 deletion. These findings suggest that although Tlr7 is upregulated in 5XFAD mice and controls spatial learning of 5XFAD mice, TLR7 is not critical in the inflammatory responses of AD brains.
Our results suggest the beneficial effect of Tlr7 deletion on the spatial learning process of 5XFAD mice, even though Aβ deposition and inflammation in the brains of 5XFAD mice are not ameliorated by Tlr7 deletion. The role of TLR7 differs from that of Tlr2 deletion in correcting AD pathological features. Thus, various TLRs likely carry out different functions and have differing or even opposite impacts on AD.