Illumination with 630 nm Red Light Reduces Oxidative Stress and Restores Memory by Photo-Activating Catalase and Formaldehyde Dehydrogenase in SAMP8 Mice.
AIMS
Pharmacological treatments for Alzheimer's disease (AD) have not resulted in desirable clinical efficacy over 100 years. Hydrogen peroxide (H2O2), a reactive and the most stable compound of reactive oxygen species, contributes to oxidative stress in AD patients. In this study, we designed a medical device to emit red light at 630 ± 15 nm from a light-emitting diode (LED-RL) and investigated whether the LED-RL reduces brain H2O2 levels and improves memory in senescence-accelerated prone 8 mouse (SAMP8) model of age-related dementia.


RESULTS
We found that age-associated H2O2 directly inhibited formaldehyde dehydrogenase (FDH). FDH inactivity and semicarbazide-sensitive amine oxidase (SSAO) disorder resulted in endogenous formaldehyde (FA) accumulation. Unexpectedly, excess FA, in turn, caused acetylcholine (Ach) deficiency by inhibiting choline acetyltransferase (ChAT) activity in vitro and in vivo. Interestingly, the 630 nm red light can penetrate the skull and the abdomen with light penetration rates of ∼49% and ∼43%, respectively. Illumination with LED-RL markedly activated both catalase and FDH in the brains, cultured cells, and purified protein solutions, all reduced brain H2O2 and FA levels and restored brain Ach contents. Consequently, LED-RL not only prevented early-stage memory decline but also rescued late-stage memory deficits in SAMP8 mice.


INNOVATION
We developed a phototherapeutic device with 630 nm red light, and this LED-RL reduced brain H2O2 levels and reversed age-related memory disorders.


CONCLUSIONS
The phototherapy of LED-RL has low photo toxicity and high rate of tissue penetration and noninvasively reverses aging-associated cognitive decline. This finding opens a promising opportunity to translate LED-RL into clinical treatment for patients with dementia. Antioxid. Redox Signal. 00, 000-000.
['Zhang|Jingnan|J|', 'Yue|Xiangpei|X|', 'Luo|Hongjun|H|', 'Jiang|Wenjing|W|', 'Mei|Yufei|Y|', 'Ai|Li|L|', 'Gao|Ge|G|', 'Wu|Yan|Y|', 'Yang|Hui|H|', 'An|Jieran|J|', 'Ding|Shumao|S|', 'Yang|Xu|X|', 'Sun|Binggui|B|', 'Luo|Wenhong|W|', 'He|Rongqiao|R|', 'Jia|Jianping|J|', 'Lyu|Jihui|J|', 'Tong|Zhiqian|Z|']
D000445:Aldehyde Oxidoreductases D000818:Animals D002374:Catalase D004195:Disease Models, Animal D005557:Formaldehyde D008027:Light D008297:Male D008568:Memory D008569:Memory Disorders D051379:Mice D018384:Oxidative Stress
oxidative stress memory formaldehyde hydrogen peroxide acetylcholine light-emitting diode with red light