Night Photostimulation of Clearance of Beta-Amyloid from Mouse Brain: New Strategies in Preventing Alzheimer’s Disease

Abstract

The deposition of amyloid-β (Aβ) in the brain is a risk factor for Alzheimer’s disease (AD). Therefore, new strategies for the stimulation of Aβ clearance from the brain can be useful in preventing AD. Transcranial photostimulation (PS) is considered a promising method for AD therapy. In our previous studies, we clearly demonstrated the PS-mediated stimulation of lymphatic clearing functions, including Aβ removal from the brain. There is increasing evidence that sleep plays an important role in Aβ clearance. Here, we tested our hypothesis that PS at night can stimulate Aβ clearance from the brain more effectively than PS during the day. Our results on healthy mice show that Aβ clearance from the brain occurs faster at night than during wakefulness. The PS course at night improves memory and reduces Aβ accumulation in the brain of AD mice more effectively than the PS course during the day. Our results suggest that night PS is a more promising candidate as an effective method in preventing AD than daytime PS. These data are an important informative platform for the development of new noninvasive and nonpharmacological technologies for AD therapy as well as for preventing Aβ accumulation in the brain of people with disorder of Aβ metabolism, sleep deficit, elderly age, and jet lag.

The effect of photobiomodulation on the brain during wakefulness and sleep

“…No previous study has examined the effect of photobiomodulation on brain wave-forms during sleep; for example, whether it influences the activity of the δ and θ waves during slow-wave sleep, as it does these waves and the α, β and γ waves during wakefulness ( Vargas et al, 2017 ; Wang et al, 2017 ; Jahan et al, 2019 ; Zomorrodi et al, 2019 ). There have, however, been recent indications that photobiomodulation does in fact impact the clearance of fluid and toxic waste more effectively during sleep than during wakefulness (e.g., Semyachkina-Glushkovskaya et al, 2021b ).…”

“…Transcranial photobiomodulation has been shown to improve the clearance of experimentally introduced substances (e.g., gold nanorods and dextran) into the cerebrospinal fluid ( Semyachkina-Glushkovskaya et al, 2020 ). In addition, photobiomodulation reduces β-amyloid accumulation and the cognitive loss of Alzheimer’s-induced mice more effectively during sleep, than during wakefulness ( Semyachkina-Glushkovskaya et al, 2021b ). It also stimulates the overall flow of cerebrospinal fluid through the brain, as well as prompting the break-up of β-amyloid aggregations ( Figure 4C ; Yue et al, 2019 ).…”

“…It also stimulates the overall flow of cerebrospinal fluid through the brain, as well as prompting the break-up of β-amyloid aggregations ( Figure 4C ; Yue et al, 2019 ). When applied to normal mice at night, photobiomodulation promotes a faster clearance of β-amyloid from the ventricular system of the brain, than when it is applied during the day ( Semyachkina-Glushkovskaya et al, 2021b ). Finally, photobiomodulation has been shown to stimulate the clearance of fluid from the meningeal lymphatic vessels; these vessels are considered crucial in the final clearance of β-amyloid from the brain ( Zinchenko et al, 2019 ).…”

“…The precise mechanisms used by photobiomodulation to stimulate the activity of the glymphatic system, that is to improve the fluid clearance and disposal of waste-products from the brain, are far from clear ( Salehpour et al, 2022 ). Previous authors have shown that photobiomodulation prompts the breakdown of various protein aggregations within the brain and stimulates a nitric oxide-induced vasodilation – at least outside the brain, within the lymphatic vessels of the meninges – and these are likely to contribute to the improved fluid and waste clearance from the brain ( Yue et al, 2019 ; Semyachkina-Glushkovskaya et al, 2020 , 2021a , 2021b , 2021c ). Many other mechanisms, as yet unknown, are, however, likely to be at play also, particular within the glymphatic system.…”

“…Although not stated explicitly in the bulk of these previous studies, many – if not all – of the photobiomodulation treatments were undertaken during daylight hours, when the experimental animals or human subjects were in a state of wakefulness. There are, however, recent indications that photobiomodulation, when applied during the state of sleep, has a somewhat different effect; that during this state, photobiomodulation stimulates the house-keeping function of the brain, by improving the clearance of fluid-filled waste-products and debris from the brain and into the lymphatic system ( Semyachkina-Glushkovskaya et al, 2021b ).…”