The progressive number of old adults with cognitive impairment worldwide and the lack of efective pharmacologic therapies require the development of non-pharmacologic strategies.The photobiomodulation(PBM)is a promisi...The progressive number of old adults with cognitive impairment worldwide and the lack of efective pharmacologic therapies require the development of non-pharmacologic strategies.The photobiomodulation(PBM)is a promising method in prevention of early or mild age-related cognitive impairments.However,it remains unclear the efcacy of PBM for old patients with signifcant age-related cognitive dysfunction.In our study on male mice,we show a gradual increase in the brain amyloid beta(Aβ)levels and a decrease in brain drainage with age,which,however,is associated with a decline in cognitive function only in old(24 months of age)mice but not in middle-aged(12 months of age)and young(3 month of age)animals.These age-related features are accompanied by the development of hyperplasia of the meningeal lymphatic vessels(MLVs)in old mice underlying the decrease in brain drainage.PBM improves cognitive training exercises and Aβclearance only in young and middle-aged mice,while old animals are not sensitive to PBM.These results clearly demonstrate that the PBM efects on cognitive function are correlated with age-mediated changes in the MLV network and may be efective if the MLV function is preserved.These fndings expand fundamental knowledge about age diferences in the efectiveness of PBM for improvement of cognitive functions and Aβclearance as well as about the lymphatic mechanisms responsible for age decline in sensitivity to the therapeutic PBM efects.展开更多
With the increase in the aging population,the global number of people with Alzheimer’s disease(AD)progressively increased worldwide.The situation is aggravated by the fact that there is no the efective pharmacologica...With the increase in the aging population,the global number of people with Alzheimer’s disease(AD)progressively increased worldwide.The situation is aggravated by the fact that there is no the efective pharmacological therapy of AD.Photobiomodulation(PBM)is non-pharmacological approach that has shown very promising results in the therapy of AD in pilot clinical and animal studies.However,the mechanisms of therapeutic efects of PBM for AD are poorly understood.In this study on mice,we demonstrate that photodynamic efects of 5-aminolevulenic acid and laser 635 nm cause reduction of network of the meningeal lymphatic vessels(MLVs)leading to suppression of lymphatic removal of beta-amyloid(Aβ)from the right lateral ventricle and the hippocampus.Using the original protocol of PBM under electroencephalographic monitoring of wakefulness and sleep stages in non-anesthetized mice,we discover that the 7-day course of PBM during deep sleep vs.wakefulness provides better restoration of clearance of Aβfrom the ventricular system of the brain and the hippocampus.Our results shed light on the mechanism of PBM and show the stimulating efects of PBM on the brain lymphatic drainage that promotes transport of Aβvia the lymphatic pathway.The efects of PBM on the brain lymphatics in sleeping brain open a new niche in the study of restorative functions of sleep as well as it is an important informative platform for the development of innovative smart sleep technologies for the therapy of AD.展开更多
基金support with the enzyme immunoassay and immunofuorescence analysis within Project No.GR 1022040700963-8(IBPPM RAS).
文摘The progressive number of old adults with cognitive impairment worldwide and the lack of efective pharmacologic therapies require the development of non-pharmacologic strategies.The photobiomodulation(PBM)is a promising method in prevention of early or mild age-related cognitive impairments.However,it remains unclear the efcacy of PBM for old patients with signifcant age-related cognitive dysfunction.In our study on male mice,we show a gradual increase in the brain amyloid beta(Aβ)levels and a decrease in brain drainage with age,which,however,is associated with a decline in cognitive function only in old(24 months of age)mice but not in middle-aged(12 months of age)and young(3 month of age)animals.These age-related features are accompanied by the development of hyperplasia of the meningeal lymphatic vessels(MLVs)in old mice underlying the decrease in brain drainage.PBM improves cognitive training exercises and Aβclearance only in young and middle-aged mice,while old animals are not sensitive to PBM.These results clearly demonstrate that the PBM efects on cognitive function are correlated with age-mediated changes in the MLV network and may be efective if the MLV function is preserved.These fndings expand fundamental knowledge about age diferences in the efectiveness of PBM for improvement of cognitive functions and Aβclearance as well as about the lymphatic mechanisms responsible for age decline in sensitivity to the therapeutic PBM efects.
基金We thank research center“Symbiosis”and immunochemistry laboratory IBPPM RAS for their support with immunofuorescence analysis and confocal microscopy within Project No.GR 121031100266-3SGO,FI,SA,BI,TA,DA,ZM,ED,AV,EA,VV,TA,KV,MM,and MA were supported by grant(No.23-75-30001)+1 种基金the Russian Science Foundation,DA and ED were supported by Grant(No.21-75-10088)the Russian Science Foundation and by Grant from the Russian Ministry of Science and High Education(No.075-15-2022-1094).
文摘With the increase in the aging population,the global number of people with Alzheimer’s disease(AD)progressively increased worldwide.The situation is aggravated by the fact that there is no the efective pharmacological therapy of AD.Photobiomodulation(PBM)is non-pharmacological approach that has shown very promising results in the therapy of AD in pilot clinical and animal studies.However,the mechanisms of therapeutic efects of PBM for AD are poorly understood.In this study on mice,we demonstrate that photodynamic efects of 5-aminolevulenic acid and laser 635 nm cause reduction of network of the meningeal lymphatic vessels(MLVs)leading to suppression of lymphatic removal of beta-amyloid(Aβ)from the right lateral ventricle and the hippocampus.Using the original protocol of PBM under electroencephalographic monitoring of wakefulness and sleep stages in non-anesthetized mice,we discover that the 7-day course of PBM during deep sleep vs.wakefulness provides better restoration of clearance of Aβfrom the ventricular system of the brain and the hippocampus.Our results shed light on the mechanism of PBM and show the stimulating efects of PBM on the brain lymphatic drainage that promotes transport of Aβvia the lymphatic pathway.The efects of PBM on the brain lymphatics in sleeping brain open a new niche in the study of restorative functions of sleep as well as it is an important informative platform for the development of innovative smart sleep technologies for the therapy of AD.
