Age as a limiting factor for the effectiveness of photostimulation of brain drainage function and cognitive abilities
Andrey V. Terskov1, Viktoria V. Adushkina1, Daria A. Zlatogorskaya1, Alexander A. Shirokov1,2, Oxana V. Semyachkina-Glushkovskaya1;
1Saratov State University, Saratov, Russia;
2Institute of Biochemistry and Physiology of Plants and Microorganisms, Russian Academy of Sciences, Saratov, Russia
Abstract
The progressive increase in life expectancy is accompanied by a rising incidence of age-related cognitive decline, for which no effective pharmacotherapy currently exists. In this context, photobiomodulation (PBM) is regarded as a promising non-pharmacological modality for the prevention and correction of cognitive disorders. Nevertheless, the question of the age-related limits of PBM efficacy, particularly in advanced age, remains unresolved.
The present study was designed to assess the efficacy of transcranial photobiomodulation in improving brain drainage, cognitive performance, and lymphatic clearance of beta-amyloid (Aβ) from the central nervous system.
The experiments were performed on male C57BL/6 mice assigned to three age groups: young (3 months), middle-aged (12 months), and old (24 months), corresponding approximately to 25, 42.5, and 69 human years. The animals underwent a 10-day course of PBM (1050 nm, 30 J/cm², pulsed mode). Cognitive function was evaluated by the rate of formation of a conditioned reflex (light–lever–food) in an operant chamber. The state of the meningeal lymphatic vessels (MLVs) was examined by confocal microscopy with immunohistochemical staining for LYVE-1. Brain drainage function was assessed by the distribution of FITC-dextran and its accumulation in the deep cervical lymph nodes. Soluble Aβ levels in the brain were quantified by ELISA.
Old mice exhibited a significantly slower rate of conditioned reflex formation compared with young and middle-aged animals (p < 0.05). The PBM course significantly improved cognitive performance in young and middle-aged mice but produced no effect in old animals. Pronounced morphological alterations of MLVs were revealed in old mice, manifesting as lymphatic hyperplasia in the region of the venous sinuses, whereas in young and middle-aged mice MLVs retained their typical architecture. Brain drainage function declined progressively with age: the distribution of FITC-dextran and its accumulation in the lymph nodes were minimal in old mice (p < 0.01). Aβ levels in the brain increased with age and were maximal in old animals. PBM effectively reduced Aβ content to the level of young animals only in middle-aged mice (p < 0.001), but did not affect this parameter in old mice.
In sum, the results revealed that the efficacy of PBM in improving cognitive functions and stimulating Aβ clearance is limited by age and is determined by the preservation of the morphological and functional state of MLVs. The lymphatic hyperplasia identified in old animals, associated with reduced brain drainage function, represents a key factor that negates the therapeutic effect of PBM. These findings substantiate the need to search for novel strategies (for example, synchronization of PBM with sleep phases) to overcome age-related resistance to phototherapeutic intervention.
The study was supported by the Russian Science Foundation, grant No. 23-75-30001
Speaker
Terskov Andrey
Saratov State University
Russia
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