A, LLLT (2 J/cm2) protects SH-SY5Y cells against A2535 (25 m) neurotoxicity using the CCK-8 assay after being irradiated with LLLT for 12 h, 24 h, or 48 h. B, Primary hippocampal neurons or SH-SY5Y cells were exposed to A2535 followed by irradiation with LLLT at 0.5 J/cm2, 1 J/cm2, 2 J/cm2, or 4 J/cm2, respectively. Anti-NT-3 antibody was purchased from R&D Systems. 3F). The human neuroblastoma cell line SH-SY5Y was cultured in DMEM containing 10% heat-inactivated fetal bovine serum, penicillin (100 Us/ml), and streptomycin (100 g/ml) in 5% CO2, 95% air at 37C in a humidified incubator. Hang Zhao, Beilei Zhu, Xuerong Huang & Zhiqian Tong Lasers in Medical Science 38, Article number: 39 ( 2023 ) Cite this article 1762 Accesses 7 Altmetric Metrics Abstract Alzheimer's disease (AD) and dementia are the most worrying health problems faced by people globally today. However, it requires further animal experiments to elucidate mechanisms of action and large, double-blind, randomized, and controlled trials to explore true efficacy in patients with ND. Before a treatment, peptides were preincubated at 37C for 5 d to promote aggregation and the diluted with medium to desired concentration (25 m). Flow cytometry was performed on a BD FACSCanto II flow cytometer (Becton Dickinson). To examine the neuroprotective effect of LLLT against A cytotoxicity, we used neuronal cell line SH-SY5Y, which is an in vitro model to mimic responses of neurons. Low intensity light stimulates nitrite-dependent nitric oxide synthesis but not oxygen consumption by cytochrome c oxidase: Implications for phototherapy. A growing body of evidence has shown that intervention with NIr light ameliorates the negative cognitive effects of AD in mouse models, restoring memory capacity and leading to a reduction in amyloid- (A) burden in the brain. The clock gene plays an important role in the circadian regulation mechanism. Staining with Rhodamine-labeled phalloidin to visualize F-actin (red). Together, these studies suggest that upregulation of BDNF with LLLT by activation of ERK/CREB pathway can ameliorate A-induced neurons loss and dendritic atrophy, thus identifying a novel pathway by which LLLT protects against A-induced neurotoxicity. Videnovic A, Noble C, Reid KJ, Peng J, Turek FW, Marconi A, et al. B, Quantitative analysis of the levels of GTP-bound Rac1 after different treatments. Patients with Various Stages of Alzheimer's disease Ivan V. Maksimovich*1 1Clinic of cardiovascular diseases named after Most Holy John Tobolsky, Building 2, Block 15, 6 Lazenki Str., 119619 Moscow, Russia *carvasc@yandex.ru ABSTRACT Background: Alzheimer's disease (AD) is the leading neurodegenerative your express consent. Increasing evidence has suggested that non-drug treatments for PD, such as BLT, physical exercise, and TMS, may be useful, cheap, and non-invasive treatment methods. may email you for journal alerts and information, but is committed This type of treatment involves exposing cells or tissue to low levels of red and near infrared light. TrkB-Fc peptide was purchased from R&D Systems. Neuroprotection of midbrain dopaminergic cells in MPTP-treated mice after near-infrared light treatment. Yoshizaki T, Tada Y, Hida A, Sunami A, Yokoyama Y, Yasuda J, et al. 21. This work is supported by the National Basic Research Program of China (2011CB910402, 2010CB732602), the Program for Changjiang Scholars and Innovative Research Team in University (IRT0829), and the National Natural Science Foundation of China (81101741, 31101028). In this study, we investigated the effects of LLLT on A-induced neurotoxicity in hippocampal neurons. Farfara D, Tuby H, Trudler D, Doron-Mandel E, Maltz L, Vassar RJ, et al. The external factors including neurotrophins (Katz and Shatz, 1996), estrogen (Sakamoto et al., 2003), and electrical activity (Vaillant et al., 2002). 6. These results indicate that LLLT-induced Ras/ERK activation dependent on the calcium release from intracellular stores. 2F,G), which produced high levels of human A40 and A42 (Wu et al., 2010). [47] To further verify the effectiveness of LT in patients with sleep disorders, another study included 11 AD patients with sleep-wakefulness disorders. Fifel K, Videnovic A. Chronotherapies for Parkinson's disease. Treatment of cultured hippocampal neurons with A2535 decreased Rac1 activity (Fig. 18. Low-level laser therapy (LLLT) has been demonstrated to regulate neuronal function both in vitro and in vivo. 14. PBM used to be called "low-level laser (or light) therapy" (LLLT) but the name was changed to reflect the fact that the term "low" was undefined, lasers were not absolutely required, and inhibition of . CREB can be phosphorylated by cAMP-dependent protein kinase A (PKA), other than ERK (Gonzalez and Montminy, 1989). 3E). *p < 0.05 versus control group; #p < 0.05 versus indicated group. 73. Motor symptoms, such as resting tremor, myotonia, bradykinesia, and postural balance disorder have significant impacts on the quality of life and prognosis of PD patients. Enter multiple addresses on separate lines or separate them with commas. Photobiomodulation preserves behaviour and midbrain dopaminergic cells from MPTP toxicity: evidence from two mouse strains. J Mol Neurosci 2015; 55:430-436. doi: 10.1007/s12031 . Effect of photobiomodulation in rescuing lipopolysaccharide-induced dopaminergic cell loss in the male Sprague-Dawley rat. The AD is a degenerative disease of the CNS characterized by progressive cognitive and behavioral impairments and occurs in the elderly and pre-senile. These results further confirmed that LLLT attenuated A-induced neurotoxicity. Domer Infrared Brain Photobiomodulation Helmet with 280 pieces of Red Infrared light diodes, powerful and easy to operate Infrared Red Photobiomodulation therapy is safer and more effective over 2000 . Helicobacter Pylori, Microbiota and Cancer, Advancements and Challenges in the Treatment of Cancer, Psoriasis and Systemic Lupus Erythematosus, Update of hot topics in neuralogic diseases. 59. H, Representative immunofluorescent images of 5 DIV hippocampal neurons under indicated treatments with MAP2 antibody to visualize dendrite (green). Amara AW, Chahine LM, Videnovic A. E, Representative Western blot assay of the p-ERK, total-ERK, GTP-Ras, and total-Ras stimulated with A2535 and/or LLLT in the presence of PD98059 (1 m) and FTS (20 m) in primary hippocampal neurons. 19KJB180007), Jiangsu Provincial Social Development Projects (Nos. Altered dendritic morphology after LLLT in A2535-treated hippocampal neurons at 5 DIV via ERK/CREB pathway. MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China. We found that LLLT increased the phosphorylated form of CREB (serine 133) in A2535-treated SH-SY5Y cells, which was reversed by pretreatment with PD98059, but not G6983 and API-2 (Fig. The absorption peaks of them appear to be different in the reduced and oxidized forms, mainly distributed in the range of the red spectrum (620760 nm) and NIr spectrum (780825 nm). 89. Aguiar S, van der Gaag B, Cortese FAB. We first characterized changes in BDNF levels in the APP/PS1 transgenic mouse model at 6 months of age (Fig. Publication of an advertisement or other product mention in JNeurosci should not be construed as an endorsement of the manufacturers claims. Low Level Laser Therapy for Dementia and Alzheimer's It has been reported that A oligomer decreases active ERK and subsequently active CREB in neuroblastoma cells and in primary neurons (Ma et al., 2007). 31. The application of LT before retiring can improve the quality of sleep and reduce the incidence of nocturnal movement. To further investigate if LLLT could upregulate BDNF expression in response to A treatment, primary hippocampal neurons were exposed to A2525 followed by LLLT. 32. The signals were detected with an ODYSSEY Infrared Imaging System (LI-COR). International Journal of Alzheimer's Disease . Keywords: Alzheimer's disease, amyloid, animal models, laser therapy, transgenic mice. Pre-conditioning with remote photobiomodulation modulates the brain transcriptome and protects against MPTP insult in mice. Similar results were obtained in SH-SY5Y cells (Fig. Learning and memory deficits exhibited by transgenic mouse models of AD can be rescued by BDNF delivery (Nagahara et al., 2009). Bright. LT as a treatment for NDs presents the advantages of being low cost and having relatively minor side effects. Indeed, inhibition of ERK or knockdown CREB prevented the increased dendritic growth by LLLT in A2535-treated hippocampal neurons (Fig. As the circadian master, SCN regulates clock gene oscillations, thus synchronizing multiple central and peripheral structures. 40. In the present study, we found that LLLT rescued neurons loss and dendritic atrophy via upregulation of BDNF in both A-treated hippocampal neurons and cultured APP/PS1 mouse hippocampal neurons. 69. Ganeshan V, Skladnev NV, Kim JY, Mitrofanis J, Stone J, Johnstone DM. 1, 7). Low-level laser therapy (LLLT) has been used to treat inflammation, tissue healing, and repair processes. We also found that LLLT rescues the decrease of dendrite length and branching by upregulation of BDNF, via the ERK/CRE-binding protein (CREB) pathway. We blocked the activity of ERK and PKA by using, respectively, PD98059 and H89. In contrast with those studies, several case-control studies have reported a total lack of effect of LT in some patients. Primary neurons were derived from hippocampal of C57BL/6 mice embryonic day 14 (E14) as previously described (Neumann et al., 1995). E, Representative immunofluorescent images of p-CREB (Ser 133) (green) in SH-SY5Y cells under the indicated treatments. Alzheimer's disease results in the . 5Department of Neurology, Suqian First Hospital, Suqian, Jiangsu 223800, China. The literature was collected from PubMed through June 2020. Scale bar, 10 m. 70. Ju YE, Lucey BP, Holtzman DM. [6] In contrast, Sonja Rutten et al[9] used bright light (10,000 lux) or a control light (200 lux) daily for 30 min in the morning and evening for at least 1 week in 83 patients and found that BLT was more effective in improving subjective sleep quality than control light. Gattoni-Celli S, Richieri S, McCarthy T, Streeter J, Kindy M.S. [56] Overall, previous studies have suggested mixed effects of LT on sleep disorders in AD patients, however, there appears to be a general trend toward a positive effect of LT on sleep. Naturally occurring autoantibodies (nAbs) against the pathologic isoform of amyloid beta (A 42) were found in body fluids and indicate a systemic B cell response that may prevent Alzheimer's disease (AD) onset.N-glycans attached to immunoglobulin G-Fab/Fc fragments are features that influence their mechanism of action. Alzheimer's Disease. 96. Gas-releasing adjuvant improves efficacy of photothermal therapy for cancer In addition, a reduction of A plaques was detected in a dose-dependent manner associated with NIr treatment. 6A,B). You may be trying to access this site from a secured browser on the server. Transcranial PBM, 1 cm above the head, 670 nm, 40 mw/cm, Dopaminergic amacrine cells and TH+ cells in retina, Transcranial PBM, 12 cm above the head, 670 nm, 90 s, 0.5 J/cm, Fos+ cells in subthalamic nucleus and zona incerta , Transcranial PBM, 12 cm above the head, 670 nm, 90 s, 5 J/cm, Partially rescue the behavioral abnormalities and mitochondrial function of pink1 mutant, Transcranial PBM, 12 cm above the head, 670 nm, 90 s, 4 times, 2 J/cm, Loss of TH+ cells stress biomarkers: increase of 4-HNE, 8-OHDG, AT-8, Implanted (lateral ventricles), 0.16 mw, 67 mw, Remote PBM (applied on the trunk and leg instead of head), 670 nm, 50 mw/cm, Effects of direct transcranial application is better than remote PBM, Transcranial PBM, 670 nm, 90 s, twice daily, 1 J/cm, Whether PBM is simultaneously, before or after the MPTP injection, MPTP induced behavioral impairment cell survival , Implanted, 670 nm, 10 mw, 25 J/5 d, 35 J/7 d, Dopaminergic cells and their terminations in SN, TH+ cells in stratum, Implanted (substantia nigra next to the midline of midbrain) 670 nm, 25/35 J, before injection: NIr delivery (5 s ON/60 s OFF); after injection: 24 h, 10 mw, Implanted (Bergma coordinate (5.6 mm, +2.9 mm, 8.5 mm) 20), continuous or pulsed, 670 nm, 0.16 mw, twice daily for 23 days, 90 s per time, total dose of 634 mJ, At the stronger power, apomorphine induced rotation, Implanted (midbrain midline), 670 nm, 10 mw, 670 nm and 810 nm (simultaneously or sequentially) 22 J, 2 days, remote PBM before MPTP injection, 670 nm, 50 mw/cm, Remote PBM before MPTP injection, 670 nm, continuous wave, 4 J/cm, increase of FOS+ neurons in putamen and caudate nucleus, 20 cm in the active treatment, and 100 cm in the placebo group, 7500 lux in the active treatment group and 950 lux in the placebo group, 15 days in the morning, 30 min daily for 1 week. As shown in Figure 4B, LLLT-induced phosphorylation of CREB was markedly attenuated by PD98059, but not by H89, suggesting that MEK/ERK signaling is obligatory for LLLT-stimulated phosphorylation of CREB in A-treated hippocampal neurons. In APP/PS1 mice, the number of A declined and the size of the protein shrunk after NIr intervention. ZDXKB2016022), Jiangsu Province Postgraduate Training Innovation Project (No. [90] Sleep disorders can reduce the quality of life and impair daytime function. D, Representative Western blot assay for detecting the dose-dependent effect of LLLT on BDNF expression after 24 h. E, Western blot was performed to detect the BDNF, nerve growth factor (NGF), and NT-3 expression after A2535 treatment with or without LLLT in primary hippocampal neurons. B, E, Quantification of primary dendrites numbers per neurons under indicated treatments. The therapeutics used for the treatment only alleviate the symptoms of AD, and sometimes present side effects which may actually aggravate the patients condition. Oueslati A, Lovisa B, Perrin J, Wagnieres G, van den Bergh H, Tardy Y, et al. HD is an ND that lacks a specific treatment. BLT led to significant improvement of tremor, UPDRS I, II, and IV, and depression in the active treatment group but not in the placebo group. The interindividual variability of transcranial magnetic stimulation effects: Implications for diagnostic use in movement disorders. [46] One such study exposed patients with AD (and related dementias) to light at 350 to 400 lux for an average of 92 min of treatment (median 102 min) per 120 min treatment session for 4 weeks, and concluded that the mean percent time awake increased from 65% during baseline to 68% during treatment. Fetveit A, Bjorvatn B. Our research may provide a feasible therapeutic approach to control the progression of AD. 64. [82] The influence of external light can also be eliminated by calculating the light using quantitative instruments. Blue. Data are from one representative experiment among at least three independent experiments and are expressed as the mean SEM. In patients with AD, neurites atrophy and synaptic loss are considered the major causes of cognitive impairment (Einstein et al., 1994; Masliah et al., 2001; Selkoe, 2002). A, Act D inhibits LLLT-induced increase in BDNF mRNA expression in A2535-treated SH-S5Y cells. ND reduces the quality of life of patients and their families. Recent evidence from animal experiments has suggested that illumination of the trunk (and not the head or eyes) still affords neuroprotective effects. 54. [37] The research team kept on evaluating whether NIr treatment had the protective effects for cerebellum in two mouse strains and the results proved the capability of NIr to ameliorate the neurodegeneration in cerebellum and possibly in any part of the brain. Effects of feeding schedule changes on the circadian phase of the cardiac autonomic nervous system and serum lipid levels. [8] However, this result may be caused by repeated measurements. Photobiomodulation inside the brain: a novel method of applying near-infrared light intracranially and its impact on dopaminergic cell survival in MPTP-treated mice. [62] Several studies have shown that light alleviates some non-motor symptoms of PD patients, such as insomnia, depression, autonomic dysfunction, and fatigue. Compared with the untreated control group, the motor function of the treated mice of both genotypes was alleviated. View Full Project Details for Low Level Laser Therapy in Alzheimers Disease. 35. In addition, dendrite growth was improved after LLLT, characterized by upregulation of Rac1 activity and PSD-95 expression, and the increase in length, branching, and spine density of dendrites in hippocampal neurons. Expressions of proteins were quantified by Western blot analysis. As shown in Figure 2E, LLLT could effectively increase BDNF protein expression, but not NGF or NT-3, even in neurons exposed to A2535. However, each specific chromophore responds to a certain range of wavelengths. We should adopt more precise cognitive function assessment methods to avoid the change of scores caused by repeated measurement. Quantification of apoptosis by Annexin-V/PI staining was performed as described previously (Liang et al., 2012). *p < 0.05 versus control group; #p < 0.05 versus indicated group. [18] In ND, changes in the secretion of MT can cause disorders in the circadian rhythm of the human body. The value is directly proportional to the number of viable cells in a culture medium. These data lead to a new hypothesis that LLLT may be capable of enhancing the generation of BDNF via CREB-mediated gene expression in A-treated hippocampal neurons. Examined 120 patients suffering from dementia. Currently, PD remains an incurable neurological disease. Dr. Amanda Smith 'Highly significant improvement' at 2 months For the trial, the researchers worked with eight participants with mild to moderate Alzheimer's disease and their caretakers, who. [27] As second messengers, they could further activate a battery of signaling pathways and transcription factors. It has been reported that Ras was activated by LLLT for the formation of LLLT-induced circular ruffles (Gao et al., 2009). Recently, there has been increasing research focus on the non-motor symptoms of PD, which include depression, sleep disorders, constipation, salivation, dysphagia, hyperhidrosis, weight loss, orthostatic hypotension, frequent micturition, sexual dysfunction, and others. Furthermore, repeated measurements with the same test may cause bias. TLT is thought to stimulate ATP production, increase mitochondrial activity, and help maintain neuronal f . 5AC). Sloane PD, Williams CS, Mitchell CM, Preisser JS, Wood W, Barrick AL, et al. Marked reduction in the levels of BDNF has occurred in AD patients (Hu and Russek, 2008; Zuccato and Cattaneo, 2009) and in APP transgenic mice, such as APPNLh and TgCRND8 mice (Peng et al., 2009; Francis et al., 2012). Although different in several ways, LT has been suggested to be effective in improving sleep disorders in patients with AD, improving sleep quality, prolonging sleep time, stabilizing the circadian rhythm, and shortening the sleep latency. [25] During this process, nitric oxide (NO) photodissociates from CCO. Chung H, Dai T, Sharma SK, Huang YY, Carroll JD, Hamblin MR. An important part of diagnosing Alzheimer's disease includes being able to explain your symptoms. 1, 2). We validated that LLLT markedly increases the p-CREB level and enhances DNA-binding activity of CREB to BDNF promoter even under A treatment in both SH-SY5Y cells and primary hippocampal neurons (Fig. Bright. Figure 3F showed that the activated transcription factors p-CREB binding to promoter region of BDNF were decreased by A2535 treatment. Some studies have suggested that upregulation of SP1 transcription activity protects against neurodegenerative disorders (Ryu et al., 2003).
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