Effect of photobiological modulation therapy on cognitive impairment and cardiovascular structure in an APP/PS1 mouse model of Alzheimer’s Disease

Abstract

AbstractBackgroundPhotobiological modulation (PBM) therapy, a form of low‐dose light therapy, is beneficial in treating various disease conditions including Alzheimer’s disease (AD). Double‐transgenic mice (APPswe/PS1dE9) develop progressive accumulation of amyloid‐β (Aβ) plaques, cognitive impairment, and alterations in cardiovascular structure and function, and represent a model of AD. Prior studies have shown that PBM therapy reduces the size and number of Aβ plaques in the neocortex and hippocampus in the mouse models of AD. The aim of this study was to investigate the effects of PBM on cardiovascular structure and function and cognitive function in the aged AD mice.MethodsSix‐month old female AD (APPswe/PS1dE9; AD‐PBM, n = 8) and wild type mice (WT‐PBM, n = 8) were exposed to near‐infrared light (wavelength 850 nm, 4.5 J/cm2, 3min/day, 5 days/week) for 6 months. Control mice (AD‐CNT, n = 6; WT‐CNT, n = 6) were placed under the PBM apparatus without turning the light on for 3min/day, 5 days/week. Cardiac parameters were measured by echocardiography. Gait analysis (DigiGait), home cage activity (HCA), and spatial working memory (indicated by alternation rate in cross maze test, CM) were assessed after 6 months of treatment. Group differences were identified by two‐way ANOVA.ResultsIn HCA test, the AD‐CNT mice exhibited circadian locomotor hyperactivity at night‐time relative to WT‐CNT mice (Figure 1A, B), which was reduced by PBM. AD‐CNT mice had lower alternation rates in CM, indicating spatial working memory impairment. PBM had minimal effect on this parameter (Table 1). The AD‐CNT vs. WT‐CNT mice manifested differences in several gait parameters, specifically, they demonstrated a lower fore propel time than WT‐CNT. PBM normalized this parameter in AD‐PBM mice to the level of WT‐CNT (Figure 1C). Both WT‐PBM and AD‐PBM mice had improved cardiovascular structure, which was demonstrated by lower relative wall thickness of left ventricle (LV) and LV mass, and higher LV volume at the end of diastole in PBM‐treated vs. correspondent CNT groups (Table 1, Figure 2).ConclusionPBM improved cardiovascular structure and AD‐associated cognitive impairment in the APP/PS1 mouse model. It is possible that more effective cardiovascular structure and function contributes to Aβ removal from the brain after PBM treatment. Supported by NIA/NIH/IRP