Ma Chenchen, Wang Zhenni, Wu Wei, Ma Xiao, Wang Laijian, Zhang Xinxin, Chen Wenjing, Kuang Xi, Li Yufei, Miao Ying, Xue Tian, Jiang Bin, Yang Yupeng
Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Chinese Academy of Sciences Key Laboratory of Brain Function and Diseases, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, China.
Department of Anatomy, Neuroscience Laboratory for Cognitive and Developmental Disorders, Medical College of Jinan University, Guangzhou, Guangdong, 510630, China.
BMC Biol. 2025 Aug 4;23(1):237. doi: 10.1186/s12915-025-02360-2.
Light flickering, a non-invasive stimulation technique over recent years, has shown a promising therapeutic potential for brain dysfunctions. However, the mechanisms by which this visual stimulus exerts its beneficial effects are largely unknown.
Here, we found that 7 days of 1 h 20 and 40 Hz light flickering promoted visual plasticity in primary visual cortex of adult mice. RNA sequencing results showed an increase in lipocalin 2 (LCN2) expression in the visual cortex following 20 or 40 Hz light flickering. By contrast, 80 Hz light flickering or constant light had no significant effect on either plasticity or LCN2 expression. LCN2 knock-down blocked light flickering-induced plasticity, while its overexpression mimicked the effects of light flickering. Moreover, the administration of minocycline blocked the plasticity induced by either light flickering or LCN2 overexpressing. Lastly, 40 Hz light flickering combined with reverse suture facilitated the recovery of the abnormal ocular dominance distribution in adult amblyopic mice.
Our data indicate that non-invasive light flickering restores visual plasticity, mediated by LCN2 and microglia, providing new insights into the mechanism of light flickering.
光闪烁作为近年来一种非侵入性刺激技术，已显示出对脑功能障碍具有有前景的治疗潜力。然而，这种视觉刺激发挥其有益作用的机制在很大程度上尚不清楚。
在此，我们发现成年小鼠初级视觉皮层中，1小时20赫兹和40赫兹的光闪烁持续7天可促进视觉可塑性。RNA测序结果显示，20赫兹或40赫兹光闪烁后，视觉皮层中脂联素2（LCN2）表达增加。相比之下，80赫兹光闪烁或持续光照对可塑性或LCN2表达均无显著影响。敲低LCN2可阻断光闪烁诱导的可塑性，而其过表达则模拟了光闪烁的效果。此外，米诺环素的给药阻断了由光闪烁或LCN2过表达诱导的可塑性。最后，40赫兹光闪烁联合反向缝合促进了成年弱视小鼠异常眼优势分布的恢复。
我们的数据表明，非侵入性光闪烁可恢复由LCN2和小胶质细胞介导的视觉可塑性，为光闪烁机制提供了新的见解。
