Near-infrared light reduces β-amyloid-stimulated microglial toxicity and enhances survival of neurons: mechanisms of light therapy for Alzheimer’s disease

Abstract

Background Low-intensity light can decelerate neurodegenerative disease progression and reduce amyloid β (Aβ) levels in the cortex, though the cellular and molecular mechanisms by which photobiomodulation (PBM) protects against neurodegeneration are still in the early stages. Microglia cells play a key role in the pathology of Alzheimer’s disease by causing chronic inflammation. We present new results concerning the PBM of both oxidative stress and microglia metabolism associated with the activation of metabolic processes by 808 nm near-infrared light. Methods The studies were carried out using healthy male mice to obtain the microglial cell suspension from the hippocampus. Oligomeric β-amyloid (1-42) was prepared and used to treat microglia cells. Light irradiation of cells was performed using diode lasers emitting at 808 nm (30 mW/cm2 for 5 min, resulting in a dose of 10 J/cm2). Mitochondrial membrane potential, ROS level studies, cell viability, apoptosis, and necrosis assays were performed using epifluorescence microscopy. Phagocytosis, nitric oxide and H2O2 production, arginase, and glucose 6-phosphate dehydrogenase activities were measured using standard assays. Cytokines, glucose, lactate, and ATP were measurements with ELISA. As our data were normally distributed, two-way ANOVA test was used. Results The light induces a metabolic shift from glycolysis to mitochondrial activity in pro-inflammatory microglia affected by oligomeric Aβ. Thereby, the level of anti-inflammatory microglia increases. This process is accompanied by a decrease in pro-inflammatory cytokines and an activation of phagocytosis. Light exposure decreases the Aβ-induced activity of glucose-6-phosphate dehydrogenase, an enzyme that regulates the rate of the pentose phosphate pathway, which activates nicotinamide adenine dinucleotide phosphate oxidases to further produce ROS. During co-cultivation of neurons with microglia, light prevents the death of neurons, which is caused by ROS produced by Aβ-altered microglia. Conclusions These original data clarify reasons for how PBM protects against neurodegeneration and support the use of light for therapeutic research in the treatment of Alzheimer’s disease. Graphical Abstract

Light, Water, and Melatonin: The Synergistic Regulation of Phase Separation in Dementia

“…Similarly, photobiomodulation employing visible red light (670 nm), non-visible near infrared (NIR, 800–1090 nm), and even far infrared (FIR, 3–25 µm) show encouraging results in the attenuation of symptoms associated with dementia including a reduction in Aβ deposition, size and number of plaque and fibril formation, clearance of misfolded proteins, increased ATP production and reduced ROS production, improved executive and cognitive functions, processing speed, memory performance, mood, energy, and sleep [ 207 , 208 , 209 , 210 , 211 , 212 , 213 , 214 , 215 , 216 , 217 ] ( Table 1 ). The proposal that red and near-infrared wavelengths may promote melatonin synthesis in mitochondria via the pathway involving nitric oxide and enhanced activity of soluble adenylyl cyclase further bolsters the synergistic relationship between light and melatonin [ 218 , 219 ].…”

“…The ability to increase adenosine triphosphate (ATP) production in mitochondria is one of the most widely accepted mechanisms behind the effectiveness of photobiomodulation in dementia and other health challenges [ 211 , 217 , 220 , 221 , 222 ]. The fact that both infrared light and melatonin increase ATP production, and the adenosine moiety of ATP which is structurally similar to melatonin is capable of solubilizing protein aggregation point to the existence of a most unexpected, dynamic relationship between NIR light and melatonin that is inextricably connected to the regulation of hydrogen bonds, viscosity, protein hydration, and protein aggregation ( Figure 1 ).…”

Current emerging novel therapies for Alzheimer's disease and the future prospects of magneto-mechanical force therapy

“…These techniques include photobiomodulation (PBM), transcranial direct current stimulation (tDCS), transcranial magnetic stimulation (TMS), deep brain stimulation (DBS), and transcranial low-intensity pulsed ultrasound (LIPUS) therapy. [32][33][34][35][36] All of these techniques rely on external electrical, optical, acoustic, magnetic, and other fields of stimulation, giving them noninvasive and spatiotemporal controllable properties. As such, brain stimulation is considered a promising strategy for AD treatment.…”

Progress of Photobiomodulation for Parkinson’s Disease

“…29 Corresponding to the two main mechanisms (α-synnuclein aggregation and mitochondrial dysfunction or failure of mitochondrial biogenesis) and a potential therapeutic target (microglial activation) in the pathogenesis of PD, PBM has correlated therapeutic effects against them respectively. PBM improves clearance of misfolding proteins (amyloid-β) in other neurodegenerative diseases (Alzheimer's disease), 30,31 boosts mitochondrial biogenesis, 19 enhances mitochondrial function, 32 and suppresses microglial activation. 30 These along with other therapeutic effects render PBM a potential treatment mean for PD.…”

“…PBM improves clearance of misfolding proteins (amyloid-β) in other neurodegenerative diseases (Alzheimer's disease), 30,31 boosts mitochondrial biogenesis, 19 enhances mitochondrial function, 32 and suppresses microglial activation. 30 These along with other therapeutic effects render PBM a potential treatment mean for PD.…”