Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 May 18;46(5):4924-4934.
doi: 10.3390/cimb46050295.

Decreased Memory and Learning Ability Mediated by Bmal1/M1 Macrophages/Angptl2/Inflammatory Cytokine Pathway in Mice Exposed to Long-Term Blue Light Irradiation

Keiichi Hiramoto  1 , Sayaka Kubo  2 , Keiko Tsuji  2 , Daijiro Sugiyama  2 , Hideo Hamano  2
Affiliations

Decreased Memory and Learning Ability Mediated by Bmal1/M1 Macrophages/Angptl2/Inflammatory Cytokine Pathway in Mice Exposed to Long-Term Blue Light Irradiation

Keiichi Hiramoto et al. Curr Issues Mol Biol. .

Abstract

Humans are persistently exposed to massive amounts of blue light via sunlight, computers, smartphones, and similar devices. Although the positive and negative effects of blue light on living organisms have been reported, its impact on learning and memory remains unknown. Herein, we examined the effects of widespread blue light exposure on the learning and memory abilities of blue light-exposed mice. Ten-week-old male ICR mice were divided into five groups (five mice/group) and irradiated with blue light from a light-emitting diode daily for 6 months. After 6 months of blue light irradiation, mice exhibited a decline in memory and learning abilities, assessed using the Morris water maze and step-through passive avoidance paradigms. Blue light-irradiated mice exhibited a decreased expression of the clock gene brain and muscle arnt-like 1 (Bmal1). The number of microglia and levels of M1 macrophage CC-chemokine receptor 7 and inducible nitric oxide synthase were increased, accompanied by a decrease in M2 macrophage arginase-1 levels. Levels of angiopoietin-like protein 2 and inflammatory cytokines interleukin-6, tumor necrosis factor-α, and interleukin-1β were elevated. Our findings suggest that long-term blue light exposure could reduce Bmal1 expression, activate the M1 macrophage/Angptl2/inflammatory cytokine pathway, induce neurodegeneration, and lead to a decline in memory.

Keywords: angiopoietin like protein 2; arginase-1; blue light; brain and muscle arnt-like 1; inducible nitric oxide synthase; interleukin-6.

PubMed Disclaimer

Conflict of interest statement

Authors S. Kubo, K. Tsuji, D. Sugiyama and H. Hamano were employed by the company Daiichi Sankyo Healthcare Co., Ltd. The authors declare that this study received funding from Daiichi Sankyo Healthcare Co., Ltd. The funder was not involved in the study design, collection, analysis, or interpretation of data; the writing of this article; or the decision to submit it for publication.

Figures

Figure 1
Figure 1
Schematic diagram of the experimental method.
Figure 2
Figure 2
Effect of long-term blue light irradiation on body weight (A), motor activity (B) memory and learning ability (C,D) of mice. The Morris water maze test (C) and step-through passive avoidance test (D) were used to the assess the memory and learning ability of mice. Data values are expressed as the mean ± standard deviation (SD) derived from five specimens. ** p < 0.01.
Figure 3
Figure 3
Effect of long-term blue light irradiation on the expression of Bmal1 (A), Cry1. (B), and Cry2 (C) in the hippocampus of mice. Western blot diagram of Bmal1, Cry1, and Cry2 with molecular weight markers (D). Data values are expressed as the mean ± standard deviation (SD) derived from five specimens. ** p < 0.01.
Figure 4
Figure 4
Effect of long-term blue light irradiation on the expression of Iba1 (A), CCR7 (B), iNOS (D), and Arg-1 (E) in the hippocampus of mice. Western blot diagram of Iba1 and CCR7 with molecular weight markers (C). Data values are expressed as mean ± standard deviation (SD) derived from five specimens. * p < 0.05; ** p < 0.01.
Figure 5
Figure 5
Effect of long-term blue light irradiation on the expression of Angptl2 (A), IL-6 (B), TNF-α (C), and IL-1β (D) in the hippocampus of the mice specimens. The values are expressed as means ± SD derived from five specimens. ** p < 0.01.
Figure 6
Figure 6
Mechanism of the effect of long-term blue light irradiation on memory and learning ability in mice.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Loh K., Redd S. Understanding and preventing computer vision syndrome. Malays. Fam. Physician. 2008;3:128–130. - PMC - PubMed
    1. Jaiswal S., Asper L., Long J., Lee A., Harrison K., Gle-Biowski B. Ocular and visual discomfort associated with smartphones, tablets and computers: What we do and do not know. Clin. Exp. Optom. 2019;102:463–477. doi: 10.1111/cxo.12851. - DOI - PubMed
    1. Ouyang X., Yang J., Hong Z., Wu Y., Xie Y., Wang G. Mechanisms of blue light-induced eye hazard and protective measures: A review. Biomed. Pharmacother. 2020;130:110577. doi: 10.1016/j.biopha.2020.110577. - DOI - PubMed
    1. Erdinest N., Berkow D. Computer vision syndrome. Harefuah. 2021;160:386–392. - PubMed
    1. Auffret E., Gomart G., Bourcier T., Gaucher D., Speeg-Schatz C., Sauer A. Digital eye strain. Symptoms, prevalence, pathophysiology, and management. J. Fr. Ophtalmal. 2021;44:1605–1610. doi: 10.1016/j.jfo.2020.10.002. - DOI - PubMed

Grants and funding