Jingnan Zhang1,2, Xiangpei Yue1, Hongjun Luo3, Wenjing Jiang1,2, Yufei Mei1,4, Li Ai1, Ge Gao5, Yan Wu6, Hui Yang5, Jieran An7, Shumao Ding7, Xu Yang7, Binggui Sun4, Wenhong Luo3, Rongqiao He1,8, Jianping Jia1,9, Jihui Lyu1,2, Zhiqian Tong1. 1. 1 Laboratory of Alzheimer's Optoelectric Therapy, Alzheimer's Disease Center, Beijing Institute for Brain Disorders, Center for Brain Disorders Research, Capital Medical University , Beijing, China . 2. 2 Center for Cognitive Disorders , Beijing Geriatric Hospital, Beijing, China . 3. 3 Central Laboratory, Shantou University Medical College , Guangdong, China . 4. 4 School of Basic Medical Sciences, Zhejiang University , Hangzhou, China . 5. 5 Department of Neurobiology, School of Basic Medical Sciences , Capital Medical University, Beijing, China . 6. 6 Department of Anatomy, School of Basic Medical Sciences , Capital Medical University, Beijing, China . 7. 7 Section of Environmental Biomedicine, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Sciences, Central China Normal University , Wuhan, China . 8. 8 State Key Laboratory of Brain & Cognitive Science, Institute of Biophysics, CAS Key Laboratory of Mental Health, University of Chinese Academy of Science, Beijing, China . 9. 9 Department of Neurology, Xuanwu Hospital of the Capital Medical University , Beijing, China .
Abstract
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.
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 ADpatients. 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.
Entities:
Keywords:
acetylcholine; formaldehyde; hydrogen peroxide; light-emitting diode with red light; memory; oxidative stress